US 20090269392A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0269392 A1 Tauber et al. (43) Pub. Date: Oct. 29, 2009

(54) DRUG DELIVERY SYSTEMAND METHODS (60) Provisional application No. 61/125,985, filed on Apr. OF USE 29, 2008. (75) Inventors: Shachar Tauber, Ozark, MO (US); Randall Fuerst, Orangevale, CA (US); Keela Davis, Springfield, MO Publication Classification (US); Lyle Bowman, Pleasanton, (51) Int. Cl. CA (US); Gary Winek, Cleveland, A6IR 9/00 (2006.01) OH (US); Joseph J. Bango, JR., A 6LX 9/70 (2006.01) New Haven, CT (US) Correspondence Address: (52) U.S. Cl...... 424/429: 424/443 LATHROP & GAGE LLP 1845 S. NATIONAL, P.O. BOX 4288 SPRINGFIELD, MO 65808-4288 (US) (57) ABSTRACT (73) Assignee: Ocugenics, LLC Electrospun fibers are utilized to improve the mechanical (21) Appl. No.: 12/490,972 characteristics of a contact lens reducing the weight and mechanical strength of the polymers from which the lenses (22) Filed: Jun. 24, 2009 are typically formed. Electrospun fibers are also utilized as a drug delivery system, both through direct use in the eye and Related U.S. Application Data by inclusion of the fibers in a contact lens. The fibers are (63) Continuation-in-part of application No. 12/416,802, loaded with therapeutic drugs by a variety of methods and filed on Apr. 1, 2009. processed by coating and cross-linking the fibers. Patent Application Publication Oct. 29, 2009 Sheet 1 of 8 US 2009/0269392 A1

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DRUG DELIVERY SYSTEMAND METHODS electrospun fiber materials. The thinner cross-section lens OF USE provides increased oxygen permeability while maintaining mechanical strength. CROSS-REFERENCE TO RELATED APPLICATIONS BRIEF DESCRIPTION OF THE DRAWINGS 0001. This is a continuation-in-part application which 0009 FIG. 1 is a scanning electron micrograph of a mat of claims priority of U.S. Non-provisional patent application fibers formed by electrospinning poly(vinyl) alcohol. Ser. No. 12/416,802 filed on Apr. 1, 2009, which claims 0010 FIG. 2 is a scanning electron micrograph of a mat of priority of U.S. Provisional Patent Application No. 61/125, fibers formed by electrospinning poly(vinyl) alcohol and crosslinked by Submersion in methanol. 985 filed on Apr. 29, 2008, which applications are incorpo 0011 FIG. 3 is a scanning electron micrograph of a mat of rated herein by reference. fibers formed by electrospinning poly(vinyl) alcohol, crosslinked by Submersion in methanol, coated with an aque BACKGROUND ous Solution of poly(vinyl) alcohol, and then crosslinked a Field of the Invention second time. 0012 FIG. 4 is a graph of the concentration of a therapeu 0002 Electrospun polymer fibers provide a material with tic drug released by a fiber mat soak-loaded with the thera a variety of favorable characteristics that may be tailored to fit peutic drug after deposition. various applications. The fibers in the electrospun materials 0013 FIG. 5 is a graph of the concentration of a therapeu provide Superior mechanical strength with reduced weight tic drug released by a fiber mat fabricated from a precursor and Volume. They also have high Surface area and porosity Solution containing the therapeutic drug and coated with poly which may be altered as desired during fabrication. (vinyl) alcohol. 0003. It is therefore desirable to provide a drug delivery 0014 FIG. 5A is a graph of the first 60 minutes of the time system utilizing electrospun polymer fibers. The drug deliv period shown in FIG. 5. ery system may utilize the fibers for insertion directly into the 0015 FIG. 6 is a graph of the concentration of a therapeu eye maintaining the concentration of the drug in the eye at an tic drug released by a fiber mat fabricated from a precursor efficacious level throughout the period of drug delivery. Solution containing the therapeutic drug coated with poly 0004. The system may also utilize an improved contact (vinyl) alcohol, and crosslinked with methanol. lens incorporating electrospun fibers with desired character (0016 FIG. 6A is a graph of the first 60 minutes of the time istics, and a system and method for delivering ophthalmic period shown in FIG. 6. drugs from the improved contact lens to an eye over an extended period of time while maintaining the concentration DETAILED DESCRIPTION of the drug in the eye at an efficacious level throughout the period of drug delivery. Electrospun Fiber Mat Fabrication 0005. It is also desirable to provide a system and method 0017. The electrospun fiber mat used in the present inven for preloading drugs in the delivery system in a manner that tion is fabricated by polymerizing electrospun fibers and allows the delivery system to be stored for an extended period loading a therapeutic drug in the fiber mat using a variety of of time. techniques, which are described below with examples. 0018. The electrospinning process typically comprises an SUMMARY OF THE INVENTION apparatus including one or more electrically-conducting liq uid dispenser, such as a stainless Steel needle, disposed adja 0006. The drug delivery system described herein utilizes cent to a collector. The liquid dispenser is held at a high both “raw' electrospun fibers and an improved contact lens as electric potential, or voltage, with respect to the collector. The the means of drug delivery. The fibers and the improved electric potential may be either alternating current (AC) or contact lens provide a drug delivery system comprising a direct current (DC), or a DC biased AC voltage. Alternatively, drug-releasing scaffold formed from a mat of electrospun a substrate for receiving the electrospun fibers may be fibers and methods for incorporating various therapeutic inserted between the conducting dispenser and the collector drugs into the mat. The fiber mat may be utilized directly in such that the fibers will be deposited on the substrate as they the eye for delivery of drugs, or incorporated into an improved are propelled from the liquid dispenser by the electric field contact lens. toward the collector. 0007. The therapeutic drugs may be loaded into the drug 0019. A solution source, or well, containing a solution of delivery system by soaking the electrospun mats in a solution the polymer and various other components which may containing the drug, or by providing the drugs in the Solution include a polymer precursor (monomer) is attached to the feeding the electrospinning process thus incorporating the electrically-conducting liquid dispenserby a fluid conducting drug into the fibers in the electrospun mat. Various processes element Such as a short tube. The polymer Solution is pro for treating the electrospun mats after loading with therapeu pelled through the dispenser at a predetermined rate, either by tic drugs are also described for improving the drug delivery gravity or by mechanical means such as a pump. As the characteristics, such as coating the mats in a polymer and Solution is dispensed through the electrically-conducting dis cross-linking the electrospun fibers. penser, the high electric potential between the dispenser and 0008. The improved contact lens described herein also the collector leads to the formation of uniform fibers which comprises a contact lens that incorporates electrospun fibers are deposited on the collector. The fibers may be micro-fibers to provide desirable physical characteristics. The improved or nano-fibers depending on the parameters of the electro contact lens may be fabricated with a thinner cross-section spinning process. As the fibers are deposited on the collector due to the increased mechanical strength and rigidity of the they overlap to form a mat, as further described below. US 2009/0269392 A1 Oct. 29, 2009

0020 Polymer solutions for use in the fiber mat fabrica 27.539 g Ultra highpurified water added to TritonX-100 tion disclosed herein include, but are not limited to, aqueous (Elgan) solutions having between 5 and 15 percent polymer by 72.459 g Ultra high purified water added to PVA (Elgan) weight. Various additives may be added to the precursor solu This is the PVA polymer mixture. Without allowing the tion to lower surface tension, or to otherwise alter the char polymer mixture to cool performing the following steps. acteristics of the solution or the electrospun fibers as desired. 0028 2. Add 2,000 ml of Vigamox to 14.141 g of the For example, surfactants, such as Triton X-100, poloxomer PVA polymer mixture and vortex stir for 1 minute. 407 or other suitable surfactant, may be added to the precur 0029. 3. Add 7.0 ml of the PVA/Vigamox solution to 2 sor solution to lower the surface tension of the solution. syringes for a total of 14.0 ml of solution. 0021 Polymers for use in the electrospinning process 0.030. 4. Electrospin the PVA/Vigamox solution from include, but are not limited to the following: poly(2-hyroxy both needles simultaneously at the following param ethylmethacrylate) (pHEMA), poly(acrylic acid) (PAA), eters: poly(methacrylic acid), poly(Vinyl pyrolidone) (PVP), poly Dispense rate: 1.8 ml/hr (N-vinyl pyrolidone) (PVP), Polyvinyl alcohol (PVA), poly 18 gauge blunt end needles (methyl methacylate) (PMMA), poly(glyceral methacrylate) Voltage: 30 kV (PGMA), Silicone Hydrogels, Fluorocarbon hydrogels, poly Travel distance: 4 in acrylamide (PAM), Silicone and 3-methacryloxy-2 hydrox Total time: 2.5 hours ypropyloxy)propylbis(trimethylsiloxy)methylsilane. Other 0.031 5. After electrospinning, the resulting mat is cut polymers may be utilized if soluble in a solvent such as water, into approximately 3.0 mg squares. methanol, ethanol, hexane, acetonitrile, or tetrahydrofuran to 0.032 6. If crosslinking is desired, soak the squares in allow the electrospinning process. If the fibers are to be uti methanol for 7 hours and allow to air dry in ambient lized in a contact lens as described below, the fibers are conditions overnight. preferably formed from a polymer that is the same as the 0033 7. Coat the squares in the remaining PVA polymer polymer to be used in the remainder of the contact lens, or a solution created in step 1 above. Before coating the polymer that has a similar index of refraction, to reduce squares, the PVA polymer Solution is heated in a round negative optical characteristics of the improved contact lens. bottom flask with attached condenser for 2 hours. Additional polymer precursor solutions are described below. 0034 8. After coating the squares in the polymer solu 0022. As the fibers are deposited on the collector they form tion, allow them to air dry in ambient conditions over a mat of overlaying fibers. In some methods of depositing the night. fibers, the collector is translated in one or more linear dimen 0035 9. If a second cross-link is desired soak the sions, or in a rotational or orbital manner, perpendicular to the squares in methanol for 7 hours and then allow them to direction of fiber deposition to increase the area over which air dry in ambient conditions overnight. the fibers are deposited and to improve the consistency of the 0036 When measuring drug release profiles the following fiber mat. procedure was utilized: 0023. After a desired period of deposition, a fiber mat of a 0037 1. Each sample mat was placed into 0.5 ml ISO certain thickness will beformed, and can be removed from the 18369 saline solution in cuvettes. electrospinning apparatus and prepared for further process 0038 2. Absorbance measurements were taken at 1, 5, 1ng. 10, 20, 60, 1440, and 2880 minutes by removing the 0024. After deposition, the fiber mat may be processed in sample mat with tweezers and measuring the absorbance several ways to improve the characteristics of the fiber mat. at 336 nm. Sample mats were immediately placed back The fiber mat may be coated with a polymer by exposing the in the sample cuvette after measurement. matto an Solution of polymer precursor. As described below, 0039. 3. Measurements were normalized by mass of the coating the fibermat alters the characteristics of the fibermat, sample mat prior to dip-coating. including the release of drugs incorporated in the fiber mat. After any chemical processing, the mats may be further pro Polymer Materials for Electrospun Fibers cessed by cutting into sections or grinding into particles. 0040 Suitable hydrophobic comonomers (a) for use in 0025. The fiber mats may also be processed by exposing electrospun fibers include, without this list being exhaustive, them to a crosslinking agent Such as ethylene glycol C-C salkyl and C-C scycloalkyl acrylates and methacry dimethacrylate (EGDMA), tetraetheylene glycol lates, C-C salkylacrylamides and -methacrylamides, acry dimethacrylate (TEGDMA), divinyl benzene (DVB), diviny lonitrile, methacrylonitrile, vinyl C-C salkanoates, lacrylamide (DVACR), or any tri-allyl crosslinking agent. C-C salkenes, C-Chaloalkenes, styrene, lower alkyl sty Methanol may be added to PVA to crosslink the polymer. The rene, lower alkyl vinyl ethers, C-Co perfluoroalkyl acrylates crosslinking process increases the mechanical stability of the and methacrylates or correspondingly partly fluorinated acry fibermat by linking adjacent fibers as they intersect randomly lates and methacrylates, C-C perfluoroalkyl-ethyl-thiocar in the fiber mat. bonylaminoethyl acrylates and methacrylates, acryloxy- and 0026. An example process for creating an electrospun methacryloxy-alkylsiloxanes, N-vinylcarbazole and fiber mat is as follows. C-Calkyl esters of maleic acid, fumaric acid, itaconic acid, 0027 1. Combine the following materials, mix, place mesaconic acid and the like. Preferred comonomers are, for over heat and stir inside round-bottom flask with example, acrylonitrile, C-C alkyl esters of vinylically unsat attached condenser for 6.5 hours. urated carboxylic acids having 3 to 5 carbon atoms, or vinyl 10 wt % PPVA+2 wt % Triton X-100+DI water esters of carboxylic acids having up to 5 carbon atoms. 11.363 g Polyvinyl alcohol (Sigma-Aldrich 99% hydro 0041. Examples of suitable hydrophobic comonomers (a) lyzed) include methyl acrylate, ethyl acrylate, propyl acrylate, iso 2.277 g Triton X-100 (Aldrich) propyl acrylate, isobutyl acrylate (IBA), isooctyl acrylate US 2009/0269392 A1 Oct. 29, 2009

(OA), isodecyl acrylate (DA), cyclohexyl acrylate, 2-ethyl case. For photopolymerization, a photoinitiator which can hexyl acrylate (EHA), methyl methacrylate, ethyl methacry initiate free radical polymerization and/or crosslinking by the late, propyl methacrylate, butyl acrylate, vinyl acetate, vinyl use of light is suitably added. Examples of this are familiar to propionate, vinyl butyrate, vinyl Valerate, styrene, chloro the expert, and specifically, Suitable photoinitiators are ben prene, vinyl chloride, vinylidene chloride, acrylonitrile, Zoin methyl ether, I-hydroxycyclohexyl phenyl ketone and 1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl Darocur and Irgacur types, preferably Darocur 11738(R) and ethyl ether, perfluorohexylethylthiocarbonylaminoethyl Darocur 29590(R). Reactive photoinitiators which can be methacrylate, isobornyl methacrylate, trifluoroethyl meth incorporated, for example, into a macromer or can be used as acrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl a special comonomer (a) are also suitable. Examples of these (meth)acrylate (HFBMA and HFBA), tris-trimethylsilyloxy are to be found in EP 632 329. The photopolymerization can silyl-propyl methacrylate (TRIS), 3-methacryloxypropyl then be triggered off by actinic radiation, for example light, in pentamethyldisiloxane and bis(methacryloxypropyl) tetram particular UV light of a suitable wavelength. The spectral ethyldisiloxane. Preferred examples of hydrophobic requirements can be controlled accordingly, if appropriate, by comonomers (a) are methyl methacrylate, IBA, HFBA, addition of suitable photosensitizers. Polymerization can be HFBMA, OA, EHA, DA, TRIS and acrylonitrile. Suitable carried out in the presence or absence of a solvent. Suitable hydrophilic comonomers (a) include, without this list being solvents are in principle all solvents which dissolve the mono conclusive, hydroxyl-substituted lower alkyl acrylates and mers used, for example water, alcohols, such as lower methacrylates, acrylamide, methacrylamide, lower alky alkanols, for example ethanol or methanol, and furthermore lacrylamides and -methacrylamides, ethoxylated acry-lates carboxylic acid amides, such as dimethylformamide, dipolar and methacrylates, hydroxyl-substituted lower alkylacryla aprotic solvents, such as dimethyl sulfoxide or methyl ethyl mides and -methacrylamides, hydroxyl-substituted lower ketone, ketones, for example acteone or cyclohexanone, alkyl vinyl ethers, sodium vinylsulfonate, sodium Styrene hydrocarbons, for example toluene, ethers, for example THF, Sulfonate, 2-acrylamido-2-methylpropanesulfonic acid, dimethoxyethane or dioxane, and halogenated hydrocarbons, N-vinylpyrrole, N-vinyl-2-pyrrolidone, 2-vinyloxazoline, for example trichloroethane, and also mixtures of suitable 2-vinyl-4,4'-dialkyloxazolin-5-one, 2- and 4-vinylpyridine, solvents, for example mixtures of water with an alcohol, for vinylically unsaturated carboxylic acids having a total of 3 to example a water/ethanol or a water/methanol mixture. 5 carbon atoms, amino-lower alkyl (where the term “amino” 0044) If appropriate, a polymer network can be intensified also includes quaternary annononium), mono-lower alky by addition of a so-called crosslinking agent, for example a lamino-lower alkyl and di-lower alkylamino-lower alkyl polyunsaturated comonomer (b). The invention furthermore acrylates and methacrylates, allyl alcohol and the like. Pre relates to a polymer comprising the polymerization product ferred comonomers are, for example, N-vinyl-2-pyrrolidone, of a macromer according to the invention with, ifappropriate, acrylamide, methacrylamide, hydroxyl-substituted lower at least one vinylic comonomer (a) and with at least one alkyl acrylates and methacrylates, hydroxyl-substituted comonomer (b). Examples of typical comonomers (b) are, for lower alkylacrylamides and -methacrylamides and vinyli example, allyl(meth)acrylate, lower alkylene glycol di(meth) cally unsaturated carboxylic acids having a total of 3 to 5 acrylate, poly lower alkylene glycol di(meth)acrylate, lower carbonatoms. Examples of suitable hydrophilic comonomers alkylene di(meth)acrylate, divinyl ether, divinyl sulfone, di (a) include hydroxyethyl methacrylate (HEMA), hydroxy or trivinylbenzene, trimethylolpropane tri(meth)acrylate, ethyl acrylate, hydroxypropyl acrylate, trimethylammonium pentaerythritol tetra(meth)acrylate, bisphenol A di(meth) 2-hydroxy-ypropyl methacrylate hydrochloride (Blemer R acrylate, methylenebis(meth)acrylamide, triallyl phthalate or MQA, for example from Nippon Oil), dimethylaminoethyl diallyl phthalate methacrylate (DMAEMA), dimethylaminoethyl methacry lamide, acrylamide, methacrylamide, N,N-dimethylacryla EXAMPLES mide (DMA), allyl alcohol, vinylpyridine, glycerol meth acrylate, N-(1.I-dimethyl-3-oxobutyl)acrylamide, N-vinyl 0045 2-pyrrolidone (NVP), acrylic acid, methacrylic acid and the like. Preferred hydrophilic comonomers (a) are 2-hydroxy ethyl methacrylate, dimethylaminoethyl methacrylate, trim Monomer? Cat Crosslinker % % % % % % ethylammonium-2-hydroxypropyl methacrylate hydrochlo ride, N,N-dimethylacrylamide and N-vinyl-2-pyrrolidone. MMA 25.5 24.2 GMA 68 0042. The polymers according to the invention are built up HEMA 93.25 90 50 in a known manner from the corresponding monomers (the NVP VP 92.7 term monomers here also including a macromer according to MAA 70 42 the invention) by a polymerization reaction with which the TEDGMA 5 .75 expert is familiar. Usually, a mixture of the abovementioned EDGMA 1 1 1 1 monomers is heated, with the addition of an agent which IPP .2 .2 AIBN 25 3 3 25 forms free radicals. Such an agent which forms free radicals PWA Fibers 5.3 7.25 is, for example, azoisobutyronitrile (AIBN), potassium per PHEMA Fibers 5.25 5 8.75 oXodisulfate, dibenzoyl peroxide, hydrogen peroxide or PVP Fibers 5 Sodium percarbonate. If the compounds mentioned are heated, for example, free radicals are then formed, by *IPP Isopropyl percarbonate homolysis, and can then, for example, initiate a polymeriza *AIBN azoisobutyronitrile tion. 0046. In each example above, electrospun fibers are made 0043 A polymerization reaction can be carried out using a by dissolving 15% of the polymer in methanol and electro photoinitiator. Photopolymerization is the term used in this spinning the fibers as described previously. The weight of US 2009/0269392 A1 Oct. 29, 2009 electrospun fiber is placed in a button mold, monomer com delivery system described herein may be created by electro position from the table added, vacuum pulled on the solution, spinning PVA onto a flat rotating collector for 4 hours at a button mold top added, and polymerized at 60°C. in an oven dispense rate of 1.8 ml per hour from an 18 gauge stainless for 24 hours followed by curing at 80° C. for 4 hours. The steel needle situated 4 inches from the collector, and held at button removed and lens machined from the buttons by mea 30 kV DC from the collector. Varying the electrospinning Suring hydration parameters on the polymerized materials. time, the dispense rate, the needle gauge, the separation between dispenser and collector, and the dispenser potential Drug Delivery System Utilizing Electrospun Fibers are within the scope of the drug delivery system described 0047. The electrospun fibers may be loaded with a thera herein, and the above described set of parameters is not lim peutic drug and utilized as a drug delivery system. The fibers iting of the drug delivery system. can be used as inserts in the eye, either separately or as a mat. 0053. In a second method of loading the drug delivery The insert can be placed in the cul-de-sac of the eye in the matrix, the PVA mat is created, and then the mat is soaked in form of dry fibers or a mat of dry fibers. This dry mat placed a solution containing the therapeutic drug. In this method, the in the eye will hydrate thereby releasing the therapeutic drug therapeutic drug must be a water Soluble drug. The amount of as the mat hydrates. The fibers can also be inserted under the drug loaded into the fiber mat is dependent, among other conjunctiva or Sclera and will slowly erode away releasing the parameters, on the Soak time, the rate of uptake of the fibers, therapeutic drug, provided the fiber is not a crosslinked poly the fiber diameter, and the concentration of drug in the Soak meric material. Solution. 0048. The fiber mats may be stored dry, as noted above, 0054 The rate of drug delivery from the fiber mats after which will minimize the loss of the therapeutic drug during placement in the eye is dependent, among other parameters, storage. This will require that residual impurities such as on the fiber diameter, the drug solubility in water, the amount monomers be kept to a minimum and that hydration time will of fiber in the mat (or lens), the amount of drug loaded in the be short. The fiber mats may also be stored in water or another fiber, and other parameters. The rate of drug delivery may also solvent, which will remove impurities from the fiber mats. be controlled by changing the polymer composition from The storage solution must also contain a sufficient concentra hydrophilic to hydrophobic, by treating the surface of the tion of the therapeutic drug to prevent the drug from dissolv fibers to change the diffusion characteristics, by cross-linking ing from the fibers while in storage. the fibers and by coating the fibers with a polymer or other 0049. This drug delivery system provides for the release of coating. ophthalmic drugs from the fiber mat to an eye over an 0055. After the mats are created by electrospinning and extended period of time, thus improving the efficacy of the Subjected to drug-loading processing, if necessary, the mats drug by maintaining atherapeutic concentration of the drug in may be coated with a polymer such as PVA by submersion in the eye for a long period of time. Known methods of deliver an aqueous solution of the polymer coating. They may also be ing drugs to an eye typically result in initially high concen crosslinked before and after the PVA coating. trations of drugs that quickly drop to levels which are too low 0056. An example of forming a fibermat for drug delivery for optimal efficacy. The electrospun fibers in the drug deliv from electrospun fibers loaded with a therapeutic drug com ery system may be loaded with appropriate drugs via several prises the following steps. Dissolve 15% PVA in 5% moxi methods described below. floxacinto methanol and electrospin into nanofibers. Place 0050. In a first method of loading the drug delivery system spun fibers in methanol containing 0.6% moxifloxacin for 2 with appropriate drugs, the drugs are mixed with the polymer hours and then dry the electrospun fibers. Form the spun Solution in the liquid well that feeds the electrospinning pro fibers into a matt and store until use as an insert to place dry cess. The concentration of the drug in the polymer Solution in the lower cul-de-sac of the eye. will vary depending on the drug used and the rate and amount 0057. A wide variety of therapeutic drugs may be spun to dispensed from the fibers when in use in the eye, and will into the fibers, so long as the drug is soluble in a solvent with need to be determined experimentally or otherwise for each the polymer Solution. Examples of various types of drugs that drug and polymer combination. Typically ranges of drug may be spun into fibers include the following and any deriva concentration in the polymer Solution may range from 0.1% tives of the therapeutically-active agents which may include, to 20% of the polymer solution. The drugs are dispensed with but not be limited to: analogs, salts, esters, amines, amides, the polymer Solution through the electrically-conducting liq alcohols and acids derived from an agent of the invention and uid dispenser, and incorporated directly into the fibers created may be used in place of an agent itself. by the electrospinning process. 0.058 Examples of the antibacterial antibiotics include, 0051 Polymer solutions for use in the drug delivery sys but are not limited to: aminoglycosides (e.g., amikacin, apra tem include, but are not limited to, aqueous solutions having mycin, arbekacin, bambermycins, butirosin, dibekacin, dihy between 5 and 15 percent polymer by weight, similar to the drostreptomycin, fortimicin(s), gentamicin, isepamicin, base polymer solution utilized in the creation of the improved kanamycin, micronomicin, neomycin, neomycin unde contact lens, with the addition of the therapeutic drug to be cylenate, netilmicin, paromomycin, ribostamycin, Sisomicin, dispensed from the contact lens. The concentration of the spectinomycin, Streptomycin, tobramycin, trospectomycin), drug in the contact lens and the rate of release in the eye are amphenicols (e.g., azidamfenicol, chloramphenicol, florfeni adjusted by altering the concentration of the drug in the poly col, thiamphenicol), ansamycins (e.g., rifamide, rifampin, mer Solution. More than onetherapeutic drug may be added to rifamycin SV, rifapentine, rifaximin), beta.-lactams (e.g., car the polymer Solution to provide an improved contact lens that bacephems (e.g., loracarbef), carbapenems (e.g., biapenem, delivers a “cocktail of drugs to the eye which may be tailored imipenem, meropenem, panipenem), cephalosporins (e.g., as necessary for the patient. cefaclor, cefadroxil, cefamandole, cefatrizine, cefazedone, 0052. As an example of fiber mat formation, without lim cefazolin, cefcapene pivoxil, cefclidin, cefdinir, cefditoren, iting the range of parameters, mats for use with the drug cefepime, cefetamet, cefixime, cefinenoxime, cefodizime, US 2009/0269392 A1 Oct. 29, 2009

cefonicid, cefoperaZone, ceforanide, cefotaxime, cefotiam, hazine, Sulfamethizole, Sulfamethomidine, Sulfamethox cefoZopran, cefpimizole, cefpiramide, cefpirome, cefpo azole, Sulfamethoxypyridazine, sulfametrole, doXime proxetil, cefprozil, cefroxadine, cefsulodin, ceftazi Sulfamidocchrysoidine, Sulfamoxole, Sulfanilamide, 4-sulfa dime, cefteram, ceftezole, ceftibuten, ceftizoxime, ceftriax nilamidosalicylic acid, n. Sup.4-sulfanilylsulfanilamide, Sul one, cefuroxime, cefuZonam, cephacetrile Sodium, family lurea, n-sulfanilyl-3,4-Xylamide, Sulfanitran, Sulfa cephalexin, cephaloglycin, cephaloridine, cephalosporin, perine, Sulfaphenazole, Sulfaproxyline, Sulfapyrazine, cephalothin, cephapirin Sodium, cephradine, pivoefalexin), Sulfapyridine, Sulfasomizole, Sulfasymazine, Sulfathiazole, cephamycins (e.g., cefbuperaZone, cefinetazole, cefininox, Sulfathiourea, Sulfatolamide, Sulfisomidine, Sulfisoxazole) cefotetan, cefoxitin), monobactams (e.g., aztreonam, caru Sulfones (e.g., acedapsone, acediasulfone, acetosulfone monam, tigemonam), oxacephems, flomoxef, moxalactam), Sodium, dapsone, diathymosulfone, glucosulfone sodium, penicillins (e.g., amdinocillin, amdinocillin pivoxil, amox Solasulfone, Succisulfone, Sulfanilic acid, p-sulfanilylbenzy icillin, amplicillin, apalcillin, aspoxicillin, azidocillin, aZlocil lamine, Sulfoxone sodium, thiazolsulfone), and others (e.g., lin, bacampicillin, benzylpenicillinic acid, benzylpenicillin clofoctol, hexedine, methenamine, methenamine anhydrom Sodium, carbenicillin, carindacillin, clometocillin, cloxacil ethylene-citrate, methenamine hippurate, methenamine man lin, cyclacillin, dicloxacillin, epicillin, fenbenicillin, floxacil delate, methenamine Sulfosalicylate, nitroxoline, taurolidine, lin, hetacillin, lenampicillin, metampicillin, methicillin xibomol). Sodium, mezlocillin, nafcillin Sodium, oxacillin, penamecil 0060 Examples of the antifungal antibiotics include, but lin, penethamate hydriodide, penicilling benethamine, peni are not limited to: polyenes (e.g., amphotericin b, candicidin, cilling benzathine, penicilling benzhydrylamine, penicilling dennostatin, filipin, fungichromin, hachimycin, hamycin, calcium, penicilling hydrabamine, penicilling potassium, lucensomycin, mepartricin, natamycin, nystatin, pecilocin, penicilling procaine, penicillinn, penicillino, penicillin V, perimycin), others (e.g., azaserine, griseofulvin, oligomy penicillin V benzathine, penicillin V hydrabamine, penimepi cins, neomycin undecylenate, pyrrolnitrin, siccanin, tuberci cycline, phenethicillin potassium, piperacillin, pivampicillin, din, viridin). propicillin, quinacillin, Sulbenicillin, Sultamicillin, talampi 0061 Examples of the synthetic antifungals include, but cillin, temocillin, ticarcillin), other (e.g., ritipenem), lincosa are not limited to: allylamines (e.g., butenafine, naftifine, mides (e.g., clindamycin, lincomycin), macrollides (e.g., terbinafine), imidazoles (e.g., bifonazole, butoconazole, azithromycin, carbomycin, clarithromycin, dirithromycin, chlordantoin, chlormidazole, clotrimazole, econazole, enil erythromycin, erythromycinacistrate, erythromycineStolate, conazole, fenticonazole, flutrimazole, isoconazole, keto erythromycin glucoheptonate, erythromycin lactobionate, conazole, lanoconazole, miconazole, omoconazole, oxicona erythromycin propionate, erythromycin Stearate, josamycin, Zole nitrate, Sertaconazole, Sulconazole, tioconazole), leucomycins, midecamycins, miokamycin, oleandomycin, thiocarbamates (e.g., tolciclate, tolindate, tolnaftate), triaz primycin, rokitamycin, rosaramicin, roXithromycin, spira oles (e.g., fluconazole, itraconazole, Saperconazole, tercona mycin, troleandomycin), polypeptides (e.g., amphomycin, Zole) others (e.g., acrisorcin, amorolfine, biphenamine, bro bacitracin, capreomycin, colistin, enduracidin, enviomycin, mosalicylchloranilide, buclosamide, calcium propionate, fusafungine, gramicidin s, gramicidin(s), mikamycin, poly chlorphenesin, ciclopirox, cloxyquin, coparaffinate, diamt myxin, pristinamycin, ristocetin, teicoplanin, thiostrepton, hazole dihydrochloride, exalamide, flucytosine, halethazole, tuberactinomycin, tyrocidine, tyrothricin, Vancomycin, vio hexetidine, loflucarban, nifuratel, potassium iodide, propi mycin, Virginiamycin, Zinc bacitracin), tetracyclines (e.g., onic acid, pyrithione, Salicylanilide, sodium propionate, Sul apicycline, chlortetracycline, clomocycline, demeclocycline, bentine, tenonitrozole, triacetin, ujothion, undecylenic acid, doxycycline, guamecycline, lymecycline, meclocycline, Zinc propionate). methacycline, minocycline, oxytetracycline, penimepicy 0062) Examples of the antineoplastic agents include, but cline, pipacycline, rollitetracycline, Sancycline, tetracycline), are not limited to: antineoplastic antibiotics and analogs (e.g., and others (e.g., cycloserine, mupirocin, tuberin). aclacinomycins, actinomycin fsub.1, anthramycin, azaserine, 0059 Examples of the synthetic antibacterials include, but bleomycins, cactinomycin, carubicin, carzinophilin, chromo are not limited to: 2,4-diaminopyrimidines (e.g., brodi mycins, dactinomycin, daunorubicin, 6-diazo-5-oxo-L-nor moprim, tetroxoprim, trimethoprim), nitrofurans (e.g., fural leucine, doxorubicin, epirubicin, idarubicin, menogaril. tadone, furazolium chloride, nifuradene, nifuratel, nifurfo mitomycins, mycophenolic acid, nogalamycin, olivomy line, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin), cines, peplomycin, pirarubicin, plicamycin, porfiromycin, quinolones and analogs (e.g., cinoxacin, ciprofloxacin, clina puromycin, streptonigrin, Streptozocin, tubercidin, Zinosta floxacin, difloxacin, enoxacin, fleroxacin, flumequine, grepa tin, Zorubicin), antimetabolites exemplified by folic acid ana floxacin, lomefloxacin, miloxacin, nadifloxacin, nalidixic logs (e.g., denopterin, edatrexate, methotrexate, piritrexim, acid, norfloxacin, ofloxacin, oxolinic acid, paZufloxacin, pteropterin, TomudeXR, trimetrexate), purine analogs (e.g., pefloxacin, pipemidic acid, piromidic acid, roSoxacin, cladribine, fludarabine, 6-mercaptopurine, thiamiprine, rufloxacin, sparfloxacin, temafloxacin, to Sufloxacin, trova thioguanine), pyrimidine analogs (e.g., ancitabine, azaciti floxacin), Sulfonamides (e.g., acetyl sulfamethoxypyrazine, dine, 6-azauridine, carmofur, cytarabine, doxifluridine, benzylsulfamide, chloramine-b, chloramine-t, dichloramine emitefur, enocitabine, floxuridine, fluorouracil, gemcitabine, t, n. Sup.2-formylsulfisomidine, n. Sup.4-beta.-d-glucosylsul tagafur). fanilamide, mafenide, 4'-(methylsulfamoyl)sulfanilanilide, 0063 Examples of the steroidal anti-inflammatory agents noprylsulfamide, phthalylsulfacetamide, phthalylsulfathiaz include, but are not limited to: 21-acetoxypregnenolone, ole, Salazosulfadimidine. Succinylsulfathiazole, Sulfabenza alclometaSone, algestone, amcinonide, beclomethasone, mide, Sulfacetamide, Sulfachlorpyridazine, Sulfachrysoidine, betamethasone, budesonide, chloroprednisone, clobetasol, Sulfacytine, Sulfadiazine, Sulfadicramide, Sulfadimethoxine, clobetasone, clocortolone, cloprednol, corticosterone, corti Sulfadoxine, Sulfaethidole, Sulfaguanidine, Sulfaguanol, Sul Sone, cortivaZol, deflazacort, desonide, desoximetaSone, dex falene, Sulfaloxic acid, Sulfamerazine, Sulfameter, Sulfamet amethasone, diflorasone, diflucortolone, difluprednate, enox US 2009/0269392 A1 Oct. 29, 2009

olone, fluazacort, flucloronide, flumethasone, flunisolide, 0068 Examples of anti-mycotic agents include, but are fluocinolone acetonide, fluocinonide, fluocortin butyl, fluo not limited to: pimaricin, fluconazole, miconazole, amphot cortolone, fluorometholone, fluperolone acetate, flupred ericin B, flucytosine, and itraconazole. nidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propi Formation of the Improved Contact Lens onate, halometaSone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, maZipredone, 0069. Once the fiber mats have been produced, they are medrysone, meprednisone, methylprednisolone, mometa incorporated into a contact lens as it is manufactured. Accept Sone furoate, paramethasone, prednicarbate, prednisolone, able contact lens polymers for use in the improved contact prednisolone 25-diethylamino-acetate, prednisolone sodium lens, include, but are not limited to polyHEMA, polyHEMA/ phosphate, prednisone, prednival, prednylidene, rimexolone, MA, polyHEMA/NVP/MMA, polyHEMA/MMA, poly tiXocortol, triamcinolone, triamcinolone acetonide, triamci HEMA/GMA, polyHEMA/PC, poly VA, polyHEMA/PVP/ nolone benetonide, and triamcinolone hexacetonide. MA, polyHEMA/PVA/MA, poly MA/PVP, and polyHEMA/ 0064. Examples of the non-steroidal anti-inflammatory PVP/MMA, Poly GMA/MMA, polyHEMA/ACR, polyAA/ agents include, but are not limited to: aminoarylcarboxylic HEMA, polyMMA/AA, polysilicone hydrogel, acid derivatives (e.g., enfenamic acid, etofenamate, flufe polyfluorocarbon hydrogel, and collagen. The lens polymeris namic acid, isonixin, meclofenamic acid, mefenamic acid, preferably a homo or co-polymer of the monomer used to niflumic acid, talniflumate, terofenamate, tolfenamic acid), form the fiber mat. arylacetic acid derivatives (e.g., aceclofenac, acemetacin, 0070. In one method of fabricating the improved contact aldlofenac, amfenac, amtolimetin guacil, bufexamac, cin lens, the lens is formed individually by curing a monomer metacin, clopirac, diclofenac sodium, etodolac, felbinac, fen composition in a mold to polymerize the composition and clozic acid, fentiazac, glucametacin, ibufenac, indomethacin, create the contact lens. The electrospun fiber mats is cut into isofeZolac, isoxepac, lonazolac, metiazinic acid, mofeZolac, appropriately-sized sections or ground into appropriately Oxametacine, piraZolac, proglumetacin, Sulindac, tiaramide, sized particles, and incorporated into the contact lens by tolimetin, tropesin, Zomepirac), arylbutyric acid derivatives inserting the mat section into the mold with the monomer (e.g., bumadizon, butibufen, fenbufen, Xenbucin), arylcar composition prior to polymerization. The fibers are then poly boxylic acids (e.g., clidanac, ketorolac, tinoridine), arylpro merized with the monomer composition and is incorporated pionic acid derivatives (e.g., alminoprofen, benoxaprofen, into the improved contact lens. In a second method of fabri bermoprofen, bucloxic acid, carprofen, fenoprofen, flunoX cating an improved contact lens, the fibers may be polymer aprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ized into a button or rod of polymer material by inserting the ketoprofen, loxoprofen, naproxen, oxaprozin, piketoprolen, fibers into the appropriate mold and curing with monomers. pirprofen, pranoprofen, protizinic acid, Suprofen, tiaprofenic The button or rod is then processed by cutting or polishing to acid, Ximoprofen, Zaltoprofen), pyrazoles (e.g., difenami produce the final improved contact lens. Zole, epirizole), pyrazolones (e.g., apaZone, benzpiperylon, 0071. The improved contact lens has superior physical feprazone, mofebutaZone, moraZone, oxyphenbutaZone, phe characteristics as a result of the addition of the electrospun nylbutaZone, pipebuZone, propyphenaZone, ramifenaZone, fibers into the lens. The improved contact lens may be fabri SuxibuZone, thiazolinobutaZone), salicylic acid derivatives cated with a thinner cross-section due to the increased (e.g., acetaminosalol, aspirin, benorylate, bromosaligenin, mechanical strength and rigidity of the electrospun fiber calcium acetylsalicylate, diflunisal, etersalate, fendosal, gen materials. The thinner cross-section of the lens provides tisic acid, glycol salicylate, imidazole salicylate, lysine ace increased oxygen permeability while maintaining mechani tylsalicylate, mesalamine, morpholine salicylate, 1-naphthyl cal strength. salicylate, olsalazine, parsalmide, phenyl acetylsalicylate, 0072 Fibers loaded with therapeutic drugs as described phenyl salicylate, Salacetamide, Salicylamide o-acetic acid, above may be used to manufacture the improved contact lens. salicylsulfuric acid, Salsalate, Sulfasalazine), thiazinecar When forming a contact lens using fibers that have been boxamides (e.g., ampiroXicam, droxicam, iSoxicam, lomoxi loaded with atherapeutic drug, the polymerization conditions cam, piroXicam, tenoxicam), E-acetamidocaproic acid, S-ad and other processing steps must be controlled to prevent enosylmethionine, 3-amino-4-hydroxybutyric acid, degradation of the therapeutic drug. amixetrine, bendazac, benzydamine, alpha.-bisabolol, buco 0073. An example of forming a contact lens from electro lome, difenpiramide, ditazol, emorfaZone, fepradinol, guaia spun fibers loaded with a therapeutic drug comprises the Zulene, nabumetone, nimeSulide, oxaceprol, paranyline, following steps. Dissolve 15% polyacrylic acid and 5% tobra perisoxal, produaZone, Superoxide dismutase, tenidap, and mycin in methanol and electrospin polyacrylic acid fibers Zileuton. containing the antibiotic. Place these fibers in a button mold 0065. Examples of anti-allergic agents include, but are not and add acrylic acid monomer, 1% EDGMA and 0.25% limited to: tranilast, ketotifen fumarate, pheniramine, diphen AIBN. Heat at 550 C. for 24 hours and cure at 850 C. for 2 hydramine hydrochloride, sodium cromoglicate, bepotastine, hours. Remove from the mold and machine into a contact epinastine HCl, olopatadine hydrochloride, levocombstine lens. Extract the residual monomers form the lens by placing HCl, and bepotastine besilate. in physiological saline containing 0.3% tobramycin for 24 0.066 Examples of glaucoma-treating agents include, but hours. Remove from extract solution, replace with fresh 0.3% are not limited to: pilocarpine hydrochloride, carbocal, tobramycin physiological saline, autoclave at 1230 C and latanoprost, travoprost, bimatoprost, betaxolol, levobunalol, store until use. timolol, iganipidine, brinzolamide, brimonidine and isopro 0074 The electrospun fibermats may be incorporated into pylunoprostone. a contact lens using other methods of contact lens fabrication. 0067 Examples of antiviral agents include, but are not The previous examples of contact lens fabrication are illus limited to: idoxuridine, acyclovir, and trifluorouridine. trative of current contact lens fabrication techniques and US 2009/0269392 A1 Oct. 29, 2009

methods of incorporating the fiber mat into those methods of What is claimed is: fabrication. They are not intended to be limiting of the present 1. A drug delivery system comprising: invention. a. at least one therapeutic drug; and 0075. The desired concentration of therapeutic drug in the b. electrospun polymer fibers; target tissue determines the amount of drug to be loaded in the c. wherein the therapeutic drugs are loaded into the elec improved contact lens. The target tissue concentration can be trospun polymer fibers. increased by adding additional fibers to the contact lens or by 2. The drug delivery system of claim 1 wherein the thera increasing the concentration of the therapeutic drug in the peutic drugs are loaded into the electrospun polymer fibers by solution from which the fibers are spun. soaking the fibers in a solution containing the therapeutic 0076 FIG. 1 is a scanning electron micrograph of a fiber drug. mat created by electrospinning poly(vinyl alcohol). The 3. The drug delivery system of claim 2 wherein the elec fibers are deposited randomly throughout the mat in various trospun fibers are soaked in a cross-linking agent. orientations. 4. The drug delivery system of claim 3 wherein the elec 0077 FIG. 2 is a scanning electron micrograph of a fiber trospun fibers are coated with a polymer. mat created by electroSpinning poly(vinyl alcohol) and 5. The drug delivery system of claim 1 wherein the thera crosslinking the resulting mat using methanol as a crosslink peutic drugs are loaded into the electrospun polymer fibers by ing agent. As can be seen in the figure, the fibers are linked at spinning the fibers from a polymer Solution containing the the intersection of overlapping fibers. therapeutic drugs. 0078 FIG. 3 is a scanning electron micrograph of a fiber 6. The drug delivery system of claim 5 wherein the polymer mat created by electroSpinning poly(vinyl alcohol) and Solution contains a polymer selected from the group consist crosslinking the resulting mat using methanol as a crosslink ing of poly(2-hyroxyethylmethacrylate) (PHEMA), poly ing agent. The mat has then been coated with PVA and (acrylic acid) (PAA), poly(methacrylic acid), poly(Vinyl crosslinked a second time. pyrolidone) (PVP), poly(N-vinyl pyrolidone) (PVP), Polyvi 007.9 The fiber mats are tested for drug release properties nyl alcohol (PVA), poly(methyl methacylate) (PMMA), poly by cutting the mats into Small pieces and placing a piece into (glyceral methacrylate) (PGMA), Silicone Hydrogels, Fluo aqueous Solution. The concentration of the drug in the solu rocarbon hydrogels, polyacrylamide (PAM), Silicone and tion is then measured over time. Since there is no mechanism 3-methacryloxy-2 hydroxypropyloxy)propylbis(trimethylsi in the solution for the removal of the drug, the concentration loxy)methylsilane, C1-C18alkyl and C3-C18cycloalkyl of the drug will increase over time to its maximum value. If acrylates and methacrylates, C3-C18alkylacrylamides and the concentration remains constant, it indicates that the fiber -methacrylamides, acrylonitrile, methacrylonitrile, vinyl mat is no longer releasing the drug. C1-C18alkanoates, C2-C18alkenes, C2-C18haloalkenes, 0080 FIG. 4 is a graph of the concentration of a therapeu styrene, lower alkyl styrene, lower alkyl vinyl ethers, tic drug released by a fiber mat soak-loaded with the thera C2-C10perfluoroalkyl acrylates and methacrylates or corre peutic drug after deposition. The concentration of the drug spondingly partly fluorinated acrylates and methacrylates, released by the Soak-loaded mat reached its maximum con C3-C12 perfluoroalkyl-ethyl-thiocarbonylaminoethyl acry centration within 5 minutes of the start of the drug release test. lates and methacrylates, acryloxy- and methacryloxy-alkyl This indicates that the soak-loaded fibermat quickly releases siloxanes, N-vinylcarbazole and C1-C12alkyl esters of all of the drug that was loaded into the mat. maleic acid, fumaric acid, itaconic acid, mesaconic acid, 0081 FIG. 5 is a graph of the concentration of a therapeu acrylonitrile, C1-C4alkyl esters of vinylically unsaturated tic drug released by a fiber mat fabricated from a precursor carboxylic acids having 3 to 5 carbon atoms, or vinyl esters of Solution containing the therapeutic drug and coated with poly carboxylic acids having up to 5 carbon atoms, methyl acry (vinyl alcohol). This figure shows that the concentration late, ethyl acrylate, propyl acrylate, isopropyl acrylate, isobu reaches its maximum value in the first hour, and thus that the tyl acrylate (IBA), isooctyl acrylate (OA), isodecyl acrylate fiber mat releases all the therapeutic drug within that time (DA), cyclohexyl acrylate, 2-ethylhexyl acrylate (EHA), period. methyl methacrylate, ethyl methacry-late, propyl methacry 0082 FIG. 5A provides detail of the increasing concen late, butyl acrylate, vinyl acetate, vinyl propionate, vinyl tration for the first hour of the test. It can be seen that the butyrate, vinyl Valerate, styrene, chloroprene, vinyl chloride, concentration increases over time, approaching its maximum vinylidene chloride, acrylonitrile, 1-butene, butadiene, meth value toward the end of the first hour. acrylonitrile, vinyl toluene, vinyl ethyl ether, perfluorohexy 0083 FIG. 6 is a graph of the concentration of a therapeu lethylthiocarbonylaminoethyl methacrylate, isobornyl meth tic drug released by a fiber mat fabricated from a polymer acrylate, trifluoroethyl methacrylate, hexafluoroisopropyl Solution containing the therapeutic drug.coated with poly methacrylate, hexafluorobutyl (meth)acrylate (HFBMA and (vinyl alcohol), and crosslinked with methanol. This figure HFBA), tris-trimethylsilyloxy-silyl-propyl methacrylate shows an increasing concentration throughout the time period (TRIS), 3-methacryloxypropylpentamethyldisiloxane and of the test, revealing that the fiber mat in this test has contin bis(methacryloxypropyl) tetramethyldisiloxane, methyl ued to release the drug throughout the test period. The final methacrylate, IBA, HFBA, HFBMA, OA, EHA, DA, TRIS, maximum concentration is in the same range as for the mats acrylonitrile, hydroxyl-substituted lower alkyl acrylates and shown in FIG. 5, however the drug was released over a much methacrylates, acrylamide, methacrylamide, lower alky longer period of time. lacrylamides and -methacrylamides, ethoxylated acry-lates 0084 FIG. 6A shows the detail of the initial 60 minutes of and methacrylates, hydroxyl-substituted lower alkylacryla the test. This period of data indicates that the concentration mides and -methacrylamides, hydroxyl-substituted lower initially quickly jumps and then begins a more steady increase alkyl vinyl ethers, Sodium vinylsulfonate, sodium Styrene over time, indicating that the fiber mat initially releases the Sulfonate, 2-acrylamido-2-methylpropanesulfonic acid, drug quickly and then slows its rate of release over time. N-vinylpyrrole, N-vinyl-2-pyrrolidone, 2-vinyloxazoline, US 2009/0269392 A1 Oct. 29, 2009

2-vinyl-4,4'-dialkyloxazolin-5-one, 2- and 4-vinylpyridine, ine, cefazedone, cefazolin, cefcapene pivoxil, cefclidin, cef vinylically unsaturated carboxylic acids having a total of 3 to dinir, cefditoren, cefepime, cefetamet, cefixime, 5 carbon atoms, amino-lower alkyl (where the term “amino” cefinenoXime, cefodizime, cefonicid, cefoperaZone, cefo also includes quaternary ammonium), mono-lower alky ranide, cefotaxime, cefotiam, cefoZopran, cefpimizole, cef lamino-lower alkyl and di-lower alkylamino-Iower alkyl piramide, cefpirome, cefpodoxime proxetil, cefprozil, acrylates and methacrylates, allyl alcohol, N-Vinyl-2-pyrroli cefroxadine, cefsulodin, ceftazidime, cefteram, ceftezole, done, acrylamide, methacrylamide, hydroxyl-substituted ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, cefuZonam, lower alkyl acrylates and methacrylates, hydroxyl-Substi cephacetrile Sodium, cephalexin, cephaloglycin, cephalori tuted lower alkylacrylamides and -methacrylamides and dine, cephalosporin, cephalothin, cephapirin Sodium, ceph vinyli-cally unsaturated carboxylic acids having a total of 3 to radine, pivoefalexin, cephamycins, cefbuperaZone, cefineta 5 carbon atoms, hydroxyethyl methacrylate (HEMA), Zole, cefininox, cefotetan, cefoxitin, monobactams, hydroxyethyl acrylate, hydroxypropyl acrylate, trimethylam aztreonam, carumonam, tigemonam, oxacephems, flomoxef. monium-2-hydroxy-ypropyl methacrylate hydrochloride, moxalactam, penicillins, amdinocillin, amdinocillin pivoxil, dimethylaminoethyl meth acrylate (DMAEMA), dimethy amoxicillin, amplicillin, apalcillin, aspoxicillin, azidocillin, laminoethyl methacrylamide, acrylamide, methacrylamide, aZlocillin, bacampicillin, benzylpenicillinic acid, benzyl N,N-dimethylacrylamide (DMA), allyl alcohol, vinylpyri penicillin Sodium, carbenicillin, carindacillin, clometocillin, dine, glycerol methacrylate, N-(1-I-dimethyl-3-oxobutyl) cloxacillin, cyclacillin, dicloxacillin, epicillin, fenbenicillin, acrylamide, N-vinyl-2-pyrrolidone (NVP), acrylic acid, floxacillin, hetacillin, lenampicillin, metampicillin, methicil methacrylic acid, 2-hydroxyethyl methacrylate, dimethy lin sodium, meZlocillin, nafcillin Sodium, oxacillin, pename laminoethyl methacrylate, trimethylammonium-2-hydrox cillin, penethamate hydriodide, penicilling benethamine, ypropyl methacrylate hydrochloride, N,N-dimethylacryla penicilling benzathine, penicilling benzhydrylamine, peni mide and N-vinyl-2-pyrrolidone. cilling calcium, penicilling hydrabamine, penicilling potas 7. The drug delivery system of claim 5 wherein the polymer sium, penicilling procaine, penicillinn, penicillino, penicil solution contains between 5 and 15 percent polymer by lin V, penicillin V benzathine, penicillin V hydrabamine, weight. penimepicycline, phenethicillin potassium, piperacillin, piv 8. The drug delivery system of claim 7 wherein the con ampicillin, propicillin, quinacillin, Sulbenicillin, Sultamicil centration of therapeutic drug in the polymer Solution is lin, talampicillin, temocillin, ticarcillin, ritipenem, lincosa between 0.01% and 20%. mides, clindamycin, lincomycin, macrollides, azithromycin, 9. The drug delivery system of claim 5 wherein the fibers carbomycin, clarithromycin, dirithromycin, erythromycin, are soaked in a cross-linking agent. erythromycin acistrate, erythromycin estolate, erythromycin 10. The drug delivery system of claim 9 wherein the fibers glucoheptonate, erythromycin lactobionate, erythromycin are coated with a polymer coating. propionate, erythromycin Stearate, josamycin, leucomycins, 11. The drug delivery system of claim 10 wherein the midecamycins, miokamycin, oleandomycin, primycin, roki coated fibers are re-soaked in a cross-linking agent after tamycin, rosaramicin, roXithromycin, spiramycin, troleando application of the polymer coating. mycin, polypeptides, amphomycin, bacitracin, capreomycin, 12. The drug delivery system of claim 1 further comprising colistin, enduracidin, enviomycin, fusafungine, gramicidins, a contact lens incorporating the electrospun polymer fibers. gramicidins, mikamycin, polymyxin, pristinamycin, ristoce 13. The drug delivery system of claim 12 wherein the fibers tin, teicoplanin, thiostrepton, tuberactinomycin, tyrocidine, are incorporated into the contact lens by inserting the fibers tyrothricin, Vancomycin, viomycin, Virginiamycin, Zinc baci into a button or rod mold in which the contact lens is formed tracin, tetracyclines, apicycline, chlortetracycline, clomocy and polymering the fibers into the button or rod. cline, demeclocycline, doxycycline, guamecycline, lymecy 14. The drug delivery system of claim 13 wherein the fibers cline, meclocycline, methacycline, minocycline, are ground into particles before they are placed into the mold. oxytetracycline, penimepicycline, pipacycline, rollitetracy 15. The drug delivery system of claim 1 wherein the at least cline, sancycline, tetracycline, cycloserine, mupirocin, one therapeutic drug is selected from the group consisting of tuberin. antibacterial antibiotic drugs, synthetic antibacterial drugs, 17. The drug delivery system of claim 15 wherein the antifungal antibiotic drugs, synthetic antifungal drugs, anti synthetic antibacterial drugs are selected from the group con neoplastic agents, steroidal anti-inflammatory agents, non sisting of 2,4-diaminopyrimidines, brodimoprim, tetroX steroidal anti-inflammatory agents, anti-allergic agents, glau oprim, trimethoprim, nitrofurans, furaltadone, furazolium coma-treating agents, antiviral agents and anti-mycotic chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, agents. nifurprazine, nifurtoinol, nitrofurantoin, quinolones and ana 16. The drug delivery system of claim 15 wherein the logs, cinoxacin, ciprofloxacin, clinafloxacin, difloxacin, antibacterial antibiotic drugs are selected from the group enoxacin, fleroxacin, flumequine, grepafloxacin, lomefloxa consisting of aminoglycosides, amikacin, apramycin, arbeka cin, miloxacin, nadifloxacin, nalidixic acid, norfloxacin, cin, bambermycins, butirosin, dibekacin, dihydrostreptomy ofloxacin, oxolinic acid, paZufloxacin, pefloxacin, pipemidic cin, fortimicins, gentamicin, isepamicin, kanamycin, micro acid, piromidic acid, roSoxacin, rufloxacin, sparfloxacin, nomicin, neomycin, neomycin undecylenate, netilmicin, temafloxacin, toSufloxacin, trovafloxacin, Sulfonamides, paromomycin, ribostamycin, Sisomicin, spectinomycin, acetyl Sulfamethoxypyrazine, benzylsulfamide, chloramine streptomycin, tobramycin, trospectomycin, amphenicols, b, chloramine-t, dichloramine t, n. Sup.2-formylsulfisomi aZidamfenicol, chloramphenicol, florfenicol, thiamphenicol, dine, n. Sup.4-beta.-d-glucosylsulfanilamide, mafenide, 4'- ansamycins, rifamide, rifampin, rifamycin SV, rifapentine, (methylsulfamoyl)sulfanilanilide, noprylsulfamide, rifaximin, beta.-lactams, carbacephems, loracarbef, carbap phthalylsulfacetamide, phthalylsulfathiazole, Salazosulfadi enems, biapenem, imipenem, meropenem, panipenem, midine, Succinylsulfathiazole, Sulfabenzamide, Sulfaceta cephalosporins, cefaclor, cefadroxil, cefamandole, cefatriz mide, Sulfachlorpyridazine, Sulfachrysoidine, Sulfacytine, US 2009/0269392 A1 Oct. 29, 2009

Sulfadiazine, Sulfadicramide, Sulfadimethoxine, Sulfadoxine, cortolone, cloprednol, corticosterone, cortisone, cortivaZol. Sulfaethidole, Sulfaguanidine, Sulfaguanol, Sulfalene, Sulfa deflazacort, desonide, desoximetaSone, dexamethasone, loxic acid, Sulfamerazine, Sulfameter, Sulfamethazine, Sul diflorasone, diflucortolone, difluprednate, enoXolone, fluaza famethizole, Sulfamethomidine, Sulfamethoxazole, Sul cort, flucloronide, flumethasone, flunisolide, fluocinolone famethoxypyridazine, Sulfametrole, Sulfamidocchrysoidine, acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluo SulfamoXole, Sulfanilamide, 4-sulfanilamidosalicylic acid, rometholone, fluperolone acetate, fluprednidene acetate, flu n. Sup.4-Sulfanilylsulfanilamide, Sulfanillylurea, n-sulfanillyl prednisolone, flurandrenolide, fluticaSone propionate, for 3,4-Xylamide, Sulfanitran, Sulfaperine, Sulfaphenazole, Sul mocortal, halcinonide, halobetasol propionate, faproxyline, Sulfapyrazine, Sulfapyridine, Sulfasomizole, Sul halometaSone, halopredone acetate, hydrocortamate, hydro fasymazine, Sulfathiazole, Sulfathiourea, Sulfatolamide, cortisone, loteprednol etabonate, maZipredone, medrysone, Sulfisomidine, Sulfisoxazole, Sulfones, acedapsone, acedia Sulfone, acetosulfone sodium, dapsone, diathymosulfone, meprednisone, methylprednisolone, mometaSone furoate, glucosulfone sodium, Solasulfone, Succisulfone, Sulfanilic paramethasone, prednicarbate, prednisolone, prednisolone acid, p-sulfanilylbenzylamine, Sulfoxone sodium, thiazolsul 25-diethylamino-acetate, prednisolone sodium phosphate, fone, clofoctol, hexedine, methenamine, methenamine anhy prednisone, prednival, prednylidene, rimexolone, tiXocortol, dromethylene-citrate, methenamine hippurate, methenamine triamcinolone, triamcinolone acetonide, triamcinolone bene mandelate, methenamine Sulfosalicylate, nitroxoline, tauro tonide, and triamcinolone hexacetonide. lidine, Xibomol. 22. The drug delivery system of claim 15 wherein the 18. The drug delivery system of claim 15 wherein the non-steroidal anti-inflammatory agents are selected from the antifungal antibiotic drugs are selected from the group con group consisting of aminoarylcarboxylic acid derivatives, sisting of polyenes, amphotericin b, candicidin, dennostatin, enfenamic acid, etofenamate, flufenamic acid, isonixin, filipin, fungichromin, hachimycin, hamycin, lucensomycin, meclofenamic acid, mefenamic acid, niflumic acid, talniflu mepartricin, natamycin, nystatin, pecilocin, perimycin, aza mate, terofenamate, tolfenamic acid, arylacetic acid deriva serine, griseofulvin, oligomycins, neomycin undecylenate, tives, aceclofenac, acemetacin, alclofenac, amfenac, amtol pyrrolnitrin, siccanin, tubercidin, viridin. metin guacil, bufexamac, cinmetacin, clopirac, diclofenac 19. The drug delivery system of claim 15 wherein the Sodium, etodolac, felbinac, fenclozic acid, fentiazac, gluca synthetic antifungal drugs are selected from the group con metacin, ibufenac, indomethacin, isofeZolac, isoxepac, lona sisting of allylamines, butenafine, naftifine, terbinafine, imi Zolac, metiazinic acid, mofeZolac, oxametacine, piraZolac, dazoles, bifonazole, butoconazole, chlordantoin, chlormiida proglumetacin, Sulindac, tiaramide, tolmetin, tropesin, Zome Zole, clotrimazole, econazole, enilconazole, fenticonazole, pirac, arylbutyric acid derivatives, bumadizon, butibufen, flutrimazole, isoconazole, ketoconazole, lanoconazole, fenbufen, Xenbucin, arylcarboxylic acids, clidanac, ketoro miconazole, omoconazole, oxiconazole nitrate, Sertacona lac, tinoridine, arylpropionic acid derivatives, alminoprofen, Zole, Sulconazole, tioconazole, thiocarbamates, tolciclate, benoxaprofen, bermoprofen, bucloxic acid, carprofen, feno tolindate, tolnaftate, triazoles, fluconazole, itraconazole, profen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, Saperconazole, terconazole, acrisorcin, amorolfine, biphe indoprofen, ketoprofen, loxoprofen, naproxen, oxaprozin, namine, bromosalicylchloranilide, buclosamide, calcium piketoprolen, pirprofen, pranoprofen, protizinic acid, Supro propionate, chlorphenesin, ciclopirox, cloxyquin, coparaffi fen, tiaprofenic acid, Ximoprofen, Zaltoprofen, pyrazoles, nate, diamthazole dihydrochloride, exalamide, flucytosine, difenamizole, epirizole, pyrazolones, apaZone, benzpipery halethazole, hexetidine, loflucarban, nifuratel, potassium lon, feprazone, mofebutaZone, moraZone, oxyphenbutaZone, iodide, propionic acid, pyrithione, salicylanilide, Sodium pro phenylbutaZone, pipebuZone, propyphenaZone, ramifena pionate, Sulbentine, tenonitrozole, triacetin, ujothion, unde Zone, SuxibuZone, thiazolinobutaZone, salicylic acid deriva cylenic acid, Zinc propionate. tives, acetaminoSalol, aspirin, benorylate, bromosaligenin, 20. The drug delivery system of claim 15 wherein the calcium acetylsalicylate, diflunisal, etersalate, fendosal, gen antineoplastic agents are selected from the group consisting tisic acid, glycol salicylate, imidazole salicylate, lysine ace of antineoplastic antibiotics and analogs, aclacinomycins, tylsalicylate, mesalamine, morpholine salicylate, 1-naphthyl actinomycin f. Sub.1, anthramycin, azaserine, bleomycins, salicylate, olSalazine, parsalmide, phenyl acetylsalicylate, cactinomycin, carubicin, carzinophilin, chromomycins, dac phenyl salicylate, Salacetamide, Salicylamide o-acetic acid, tinomycin, daunorubicin, 6-diazo-5-oxo-L-norleucine, salicylsulfuric acid, Salsalate, Sulfasalazine, thiazinecarboxa doxorubicin, epirubicin, idarubicin, menogaril, mitomycins, mides, ampiroXicam, droxicam, isoxicam, lomoxicam, mycophenolic acid, nogalamycin, olivomycines, peplomy piroXicam, tenoxicam, E-acetamidocaproic acid, S-adenosyl cin, pirarubicin, plicamycin, porfiromycin, puromycin, Strep methionine, 3-amino-4-hydroxybutyric acid, amixetrine, tonigrin, Streptozocin, tubercidin, Zinostatin, Zorubicin, anti bendazac, benzydamine, alpha.-bisabolol, bucolome, difen metabolites, folic acid analogs, denopterin, edatrexate, piramide, ditazol, emorfaZone, fepradinol, guaiaZulene, methotrexate, piritrexim, pteropterin, TomudeXR, trimetrex nabumetone, nimeSulide, oxaceprol, paranyline, perisoxal, ate, purine analogs, cladribine, fludarabine, 6-mercaptopu produaZone, Superoxide dismutase, tenidap, and Zileuton. rine, thiamiprine, thioguanine, pyrimidine analogs, ancitab 23. The drug delivery system of claim 15 wherein the ine, azacitidine, 6-azauridine, carmofur, cytarabine, anti-allergic agents are selected from the group consisting of doxifluridine, emitefur, enocitabine, floxuridine, fluorou tranilast, ketotifen fumarate, pheniramine, diphenhydramine racil, gemcitabine, tagafur. hydrochloride, sodium cromoglicate, bepotastine, epinastine 21. The drug delivery system of claim 15 wherein the HCl, olopatadine hydrochloride, levocombstine HCl, and steroidal anti-inflammatory agents are selected from the bepotastine besilate. group consisting of 21-acetoxypregnenolone, alclometaSone, 24. The drug delivery system of claim 15 wherein the algestone, amcinonide, beclomethasone, betamethasone, glaucoma-treating agents are selected from the group consist budesonide, chloroprednisone, clobetasol, clobetaSone, clo ing of pilocarpine hydrochloride, carbocal, latanoprost, tra US 2009/0269392 A1 Oct. 29, 2009 voprost, bimatoprost, betaxolol, levobunalol, timolol, igani a. Soaking the fibers in a cross-linking agent for a period of pidine, brinzolamide, brimonidine and time; and isopropylunoprostone. b. coating the fibers with a polymer coating. 25. The drug delivery system of claim 15 wherein the 30. The method of claim 29 further comprising the step of antiviral agents are selected from the group consisting of soaking the fibers in a cross-linking agent for a second period idoxuridine, acyclovir, and trifluorouridine. of time. 26. The drug delivery system of claim 15 wherein the 31. The method of claim 29 wherein the step of preparing anti-mycotic agents are selected from the group consisting of the electrospun fibers further comprises the step of incorpo pimaricin, fluconazole, miconazole, amphotericin B, flucy rating the fibers into a contact lens by adding the fibers to the tosine, and itraconazole. lens before it is polymerized. 27. A method of delivering atherapeutic drug to a recipient 32. The method of claim 27 wherein the step of placing the comprising the steps of fibers in the eye of a recipient further comprises placing the a. preparing electrospun fibers loaded with at least one fibers in the cul-de-sac, the conjunctiva or Sclera of the eye. therapeutic drug; 33. A drug delivery system comprising: b. placing the fibers in the eye of the recipient of the a. a plurality of electrospun fibers; therapeutic drug; b. at least one therapeutic drug loaded into the electrospun fibers: c. naturally or artificially hydrating the electrospun fibers 34. The drug delivery system of claim 33 wherein the to release the therapeutic drug from the electrospun therapeutic drugs are loaded into the electrospun fibers by fibers. electrospinning the fibers from a polymer Solution containing 28. The method of claim 27 wherein the step of preparing the therapeutic drugs. the electrospun fibers further comprises the steps of: 35. The drug delivery system of claim 33 wherein the a. preparing a polymer Solution containing the therapeutic therapeutic drugs are loaded into the electrospun fibers by drugs; and soaking the fibers in a solution containing the therapeutic b. electrospining the fibers from the polymer solution. drugs. 29. The method of claim 28 wherein the step of preparing the electrospun fibers further comprises the steps of: