DOCSLIB.ORG

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia pharmaceutics Article Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia Jackson Russo 1 , Jennifer Fiegel 2 and Nicole K. Brogden 1,3,* 1 Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA 52242, USA; [email protected] 2 Department of Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA 52242, USA; jennifer-fi[email protected] 3 Department of Dermatology, The University of Iowa, Iowa City, IA 52242, USA * Correspondence: [email protected] Received: 12 November 2020; Accepted: 11 December 2020; Published: 15 December 2020 Abstract: Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site. Keywords: topical; poloxamer; thermogelation; chronic wounds; analgesia 1. Introduction The skin is the largest organ of the body and is key to maintaining homeostasis, with a unique layered structure that provides a barrier to harmful external materials and maintains body temperature and moisture [1–3]. However, as the body’s most exposed organ, the skin is also prone to external insults that can create open wounds and compromise its critical homeostatic functions. While most wounds heal in a timely manner, around 6.5 million Americans annually suffer from chronic wounds that undergo a greatly prolonged healing process [4]. Pain management correlates with shortened wound healing times and improved patient outcomes and thus is key to improving the quality of life for patients suffering from chronic wounds [5–8]. Systemic analgesic compounds such as orally administered non-steroidal anti-inflammatory drugs (NSAIDs) and opioids can provide pain relief. However, ongoing administration of these compounds Pharmaceutics 2020, 12, 1214; doi:10.3390/pharmaceutics12121214 www.mdpi.com/journal/pharmaceutics PharmaceuticsPharmaceutics2020 2020, 12, ,12 1214, x FOR PEER REVIEW 2 of2 of 18 19 drugs (NSAIDs) and opioids can provide pain relief. However, ongoing administration of these overcompounds the duration over ofthe a duration prolonged of a treatmentprolonged course treatment can course lead to can adverse lead to eadverseffects. effects. Prolonged Prolonged oral administrationoral administration of NSAIDs of NSAIDs is associated is associated with with peptic peptic ulcer ulcer formation formation and and renal renal failure, failure, particularly particularly inin elderly elderly patients. patients. Long-term Long-term administration administration of of systemic systemic opioids opioids is is associated associated with with constipation, constipation, respiratoryrespiratory depression, depression, and and potential potential for for addiction addiction and and misuse misuse [9, 10[9,10].]. AA topical topical analgesic analgesic product product would would limit limit systemic systemic exposure exposure and and mitigate mitigate systemic systemic adverse adverse eff effectsects whilewhile providing providing localized localized pain pain management management in in the the wound. wound. However, However, the the administration administration of of a topicala topical productproduct is likelyis likely to to involve involve prolonged prolonged wound wound site site contact, contact, which which could could increase increase the the pain pain involved involved in in woundwound dressing dressing changes changes [11 [11,12].,12]. Administration Administration of of a therapeutica therapeutic compound compound directly directly into into a wounda wound cancan also also result result in in rapid rapid absorption absorption of of the the drug drug due due to to the the lack lack of of a skina skin barrier, barrier, which which would would diminish diminish locallocal analgesic analgesic effi efficacycacy [13 [13].]. In In order order to to reduce reduce the the frequency frequency of of analgesic analgesic reapplication reapplication and and dressing dressing changes,changes, and and limit limit rapid rapid systemic systemic absorption, absorption, it it is is importantimportant thatthat aa drugdrug depot source is is provided provided to tooffer offer prolonged local deliverydelivery ofof thethe analgesicanalgesic compound.compound. AA productproduct thatthat can can be be applied applied with with minimalminimal contact contact to to the the wound wound site site itself itself while while providing providing a slow-releasea slow-release depot depot of of an an analgesic analgesic drug drug wouldwould therefore therefore be be a significanta significant advance advance in in the the optimization optimization of chronicof chronic wound wound pain pain management. management. ThermosensitiveThermosensitive polymers polymers that that undergo undergo reverse reverse thermal thermal gelation gelation are are well well suited suited to to meet meet the the uniqueunique challenges challenges presented presented by by chronic chronic wounds. wounds. Reverse Reverse thermal thermal gelation gelation is is the the process process by by which which a a polymerpolymer transitions transitions from from a liquid a liquid state state at at low low temperatures temperatures to to a gela gel state state when when heated heated [14 [14]—the]—the liquid liquid toto gel gel transition transition of poloxamer of poloxamer 407 is 407 shown is shown in Figure in 1Figure. Polymers 1. Polymers that undergo that reverseundergo thermal reverse gelation thermal couldgelation be administered could be administered as cool liquids as cool with liquids minimal with wound minimal site contact, wound and site a contact, gel would and form a gel within would theform wound within site the to provide wound asite local to depotprovide source a local of thedepot analgesic. source Poloxamerof the analgesic. 407 is aPoloxamer thermosensitive 407 is a polymerthermosensitive vehicle that polymer has low vehicle toxicity, that lack has of low skin toxici irritation,ty, lack and of reverse skin irritation, thermal gelationand reverse properties. thermal Ingelation addition, properties. poloxamer In 407 addition, systems containingpoloxamer a 407 variety systems of drug containing compounds, a variety including of drug small-molecule compounds, drugsincluding and proteins, small-molecule have been drugs shown and proteins, to remain have stable been as solutionsshown to whenremain stored stable at as 4 solutions◦C for up when to 3 monthsstored at [15 4 ,°C16]. for It up has to been 3 months studied [15,16]. for use It in has transdermal been studied delivery, for use often in transdermal in combination delivery, with eitheroften in permeationcombination enhancers with either or microneedles, permeation enhancers to overcome or themicroneedles, barrier properties to overcome of the the skin barrier [17]. However, properties poloxamerof the skin 407 [17]. is However, similarly promisingpoloxamer for407 use is simila in therly delivery promising of analgesicsfor use in the to chronicdelivery wounds of analgesics by prolongingto chronic release wounds of by a topically prolonging administered release of a analgesic topically compound administered to aanalgesic site that compound does not have to a an site intactthat skindoes barrier. not have an intact skin barrier. FigureFigure 1. 1.Solution Solution of of 20% 20%w/ ww/wpoloxamer poloxamer 407 407 in in water water (A )(A at) 4at◦ 4C °C prior prior to to heating heating and and (B ()B after) after heating heating onon a stira stir plate plate until until gelation gelation occurred, occurred, causing causing the the stir stir bar bar to stopto stop moving. moving. Past studies have been conducted exploring thermosensitive polymers as potential formulation ingredients to deliver analgesic compounds, but the delivery of an analgesic compound topically to a chronic wound site has not yet been adequately explored. A series of studies was conducted to Pharmaceutics 2020, 12, 1214 3 of 18 Past studies have been conducted
Load more

Recommended publications
  • Formulation of Poloxamers for Drug Delivery
    Journal of Functional Biomaterials Review Formulation of Poloxamers for Drug Delivery Andrew M. Bodratti and Paschalis Alexandridis * Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-716-645-1183 Received: 18 December 2017; Accepted: 14 January 2018; Published: 18 January 2018 Abstract: Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective. Keywords: Pluronic; poly(ethylene oxide); poly(ethylene glycol); nanomedicine; excipient; formulation; solubilization; anticancer; micelle; nanoparticle; hydrogel 1.
    [Show full text]
  • Poloxamer Hydrogels for Biomedical Applications
    pharmaceutics Review Poloxamer Hydrogels for Biomedical Applications Eleonora Russo * and Carla Villa Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genova, Italy; [email protected] * Correspondence: [email protected] Received: 31 October 2019; Accepted: 6 December 2019; Published: 10 December 2019 Abstract: This review article focuses on thermoresponsive hydrogels consisting of poloxamers which are of high interest for biomedical application especially in drug delivery for ophthalmic, injectable, transdermal, and vaginal administration. These hydrogels remain fluid at room temperature but become more viscous gel once they are exposed to body temperature. In this way, the gelling system remains at the topical level for a long time and the drug release is controlled and prolonged. Poloxamers are synthetic triblock copolymers of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO), also commercially known as Pluronics®, Synperonics® or Lutrol®. The different poloxamers cover a range of liquids, pastes, and solids, with molecular weights and ethylene oxide–propylene oxide weight ratios varying from 1100 to 14,000 and 1:9 to 8:2, respectively. Concentrated aqueous solutions of poloxamers form thermoreversible gels. In recent years this type of gel has arouse interest for tissue engineering. Finally, the use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC). This property is exploited for drug delivery and different therapeutic applications. Keywords: poloxamer; hydrogels; micelle; thermosensitive; biomedical; copolymer 1. Introduction The word “hydrogel”, according to Lee, Kwon and Park is due to an article published in 1894, but the first crosslinked network material that appeared in literature and that has been described by its typical hydrogel properties, was a polyhydroxyethylmethacrylate (HEMA) hydrogel developed much later, in 1960, by O.
    [Show full text]
  • ABSTRACT CHANG, DAVID W. Investigation of Interfacial
    ABSTRACT CHANG, DAVID W. Investigation of Interfacial Interactions in Surfactant-mediated Shear Protection of Animal Cell Culture (under the direction of Dr. Orlin D. Velev). The biotechnology industry has rapidly developed over the past few decades as innovative treatments for diseases and conditions emerge. This progress has led to rapid expansion of technologies to support the large scale (>10000L) production of therapeutics from microbial, fungal, mammalian, and insect cell culture. Progress in strain engineering and media optimization has led to more than hundred-fold increases in yield and productivity. However, significant gaps in knowledge still exist on the physical and interfacial phenomena involved during the upstream production process. These include fundamental understanding of interactions between cells, surfactants, and proteins, as well as the formation and mitigation of foams stabilized by bioparticles. Improper control of these interactions can hinder cell growth through shear damage, mass transfer limitations, and cell aggregation. This dissertation investigates the impact of surfactants (Poloxamers) on the gas, liquid, and cell membrane interfaces to elucidate the mechanism of surfactant-mediated protection of cell culture. We then apply this knowledge to improve bioreactor performance in a commercial Chinese Hamster Ovary (CHO) cell process. First, we characterize the foam stability and equilibrium surface tension of pure and mixed Poloxamer systems in correlation with their ability to mitigate shear damage to cells in a turbulent environment. We demonstrate that while Poloxamer 188 (P188) can function as a highly effective shear protectant, the presence of a surface-active contaminant can greatly hinder its protective characteristics. Poloxamer 407 (P407) was found to function as such a surface active “impurity,” disrupting shear protection when mixed with P188 by preferentially adsorbing to the gas-liquid and membrane-liquid interface.
    [Show full text]
  • Early-Stage Atherosclerosis in Poloxamer 407
    Korolenko et al. Lipids in Health and Disease (2016) 15:16 DOI 10.1186/s12944-016-0186-7 RESEARCH Open Access Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions Tatyana A. Korolenko1, Thomas P. Johnston2*, Fedor V. Tuzikov3,4, Natalia A. Tuzikova3,4, Alexandr B. Pupyshev6, Victor K. Spiridonov1, Natalya V. Goncharova1, Igor V. Maiborodin7 and Natalia A. Zhukova5 Abstract Background: The aims of this study were to evaluate the effect of poloxamer 407 administration on atherogenic serum lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids, as well as the onset of early atherosclerosis, in mice. Methods: Mice were administered either sterile saline or poloxamer 407 (to induce a dose-controlled hyperlipidemia) for 1 month and then sacrificed at 1, 4 and 10 days after the last dose of poloxamer 407. Systolic and diastolic blood pressure, the activity of a cysteine protease (cathepsin B) in cardiac and liver tissue, and histological/morphological examination of heart and liver specimens was performed for each group of mice at each time point. Lastly, small angle X-ray scattering was utilized to analyze the lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids for both groups of mice at each time point. Statistical analysis was performed using one-way, analysis-of-variance with post hoc analysis to determine significantly different mean values, while correlation analysis employed the Spearman test. Results: Poloxamer 407-treated mice revealed significant hyperlipidemia, moderately elevated blood pressure, general lipidosis in liver cells, increased cysteine protease activity in heart tissue, and contractile-type changes in cardiomyocytes.
    [Show full text]
  • WO 2016/095083 Al O
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/095083 Al 23 June 2016 (23.06.2016) P O P CT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 8/20 (2006.01) A61K 8/19 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K /27 (2006.01) A61Q 11/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/CN2014/093826 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 15 December 2014 (15. 12.2014) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: COLGATE-PALMOLIVE COMPANY (84) Designated States (unless otherwise indicated, for every [US/US]; 300 Park Avenue, New York 10022 (US). kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (72) Inventor; and TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant (for SC only): XV, Yun [US/CN]; 338 Qingni- TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, an Road, Xingang Huangpu, GETDD, Guangzhou, Guang DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, dong 510730 (CN).
    [Show full text]
  • Influence of Poloxamer 407 on Fractional and Subfractional Composition of Serum Lipoproteins of Mice
    Vol.2, No.7, 722-730 (2010) Health doi:10.4236/health.2010.27110 Influence of poloxamer 407 on fractional and subfractional composition of serum lipoproteins of mice Tatyana A. Korolenko1*, Fedor V. Tuzikov2,3, Thomas P. Johnston4, Natalia A. Tuzikova2,3, Elena E. Filjushina1, Viktoriya M. Loginova1, Natalia G. Savchenko1 1Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia; *Corresponding Author: [email protected] 2Boreskov Institute of Catalysis, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia 3Novosibirsk State University, Novosibirsk, Russia 4University of Missouri-Kansas City, Kansas City, USA Received 4 March 2010; revised 22 March 2010; accepted 25 March 2010. ABSTRACT Serum Lipoprotein Fractions and Subfractions Using a novel small-angle X-ray scattering (SAXS) method for determination of fractional and sub- 1. INTRODUCTION fractional composition of lipoproteins (LPs), a significant elevation of total cholesterol-lipop- Changes of different classes of circulating lipoproteins roteins (C-LP) and, especially, total triglyceride- are the important indicies of lipid metabolism in physi- lipoproteins (TG-LP), was shown in this work. ology and pathology; lipoproteins have been shown to Among the LP fractions, poloxamer 407 was also play a regulatory role in vivo [1,2]. The main lipo- shown to significantly increase proatherogenic protein classes consist of pro-atherogenic low-density li- total C-LDL, TG-LDL and, especially, their pre- poproteins (LDL), very-low-density lipoproteins (VLDL), cursors C-VLDL and TG-VLDL, while only ex- and anti-atherogenic high density lipoproteins (HDL), hibiting a moderate increase in the antiathero- and are widely used as common lipid biomarkers in genic C-HDL and TG-HDL fractions.
    [Show full text]
  • Competitive Comparison 3M™ Clinpro™ Toothpaste
    Competitive Comparison 3M™ Clinpro™ Toothpaste Fluoride Calcium Rx Is it a Product Size Flavors Type and Phosphate Full Ingredient List Manufacturer’s Claims Required? Toothpaste? Concentration Based Additive Manufactured by 3M • Clinically proven prescription-strength toothpaste • Remineralizes lesions throughout— not just on the surface • Delivers more fluoride to the tooth than other leading brands tested • Contains 1.1.% NaF (5000ppm fluoride ion) Sodium fluoride, water, sorbitol, hydrated silica, 3M™ Clinpro™ Functionalized • Contains tri-calcium phosphate ingredient (TCP), Vanilla Mint, 1.1% Sodium glycerin, polyethylene-polypropylene glycol, 5000 4oz Tricalcium so Clinpro 5000 toothpaste releases a high Yes Yes Spearmint, Fluoride flavor, polyethylene glycol, sodium lauryl sulfate, Anti-Cavity (113g) Phosphate level of fluoride plus calcium and phosphate— Bubble Gum (5000ppm) titanium dioxide, carboxymethyl cellulose, Toothpaste (fTCP) components found naturally in saliva sodium saccharin and tri-calcium phosphate • Gentle cleaning, gentle whitening • Low abrasion • Use once daily in place of a conventional toothpaste • Available in a convenient 4oz flip-top tube (approx. 6-month patient supply) • Strengthens teeth better than leading brands • Lower fluoride, no prescription needed • Exclusive formula protects against cavities Sodium fluoride, water, sorbitol, hydrated silica, 3M™ Clinpro™ Functionalized and helps reverse white spots 0.21% Sodium glycerin, polyethylene-polypropylene glycol, Tooth Crème 4oz Tricalcium • Perfect for patients at moderate or high risk No Yes Vanilla Mint Fluoride flavor, polyethylene glycol, sodium lauryl sulfate, Anti-Cavity (113g) Phosphate of dental cavities (950ppm) titanium dioxide, carboxymethyl cellulose, Toothpaste (fTCP) sodium saccharin and tri-calcium phosphate • Cleans and whitens teeth with low abrasion • Contains fluoride as well as calcium and phosphate, which are components naturally found in saliva Information available on competitive websites as of March 2019.
    [Show full text]
  • Amphiphilic and Thermoresponsive Block Copolymers Based on Hydroxypropyl Methyl Cellulose As Nano-Carrier of Hydrophobic Drugs Aijing Lu
    Amphiphilic and thermoresponsive block copolymers based on hydroxypropyl methyl cellulose as nano-carrier of hydrophobic drugs Aijing Lu To cite this version: Aijing Lu. Amphiphilic and thermoresponsive block copolymers based on hydroxypropyl methyl cellu- lose as nano-carrier of hydrophobic drugs. Material chemistry. Université Montpellier, 2020. English. NNT : 2020MONTS010. tel-03021310 HAL Id: tel-03021310 https://tel.archives-ouvertes.fr/tel-03021310 Submitted on 24 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Délivré par Université de Montpellier Préparée au sein de l’école doctorale Sciences Chimiques Balard ED 459 Et de l’unité de recherche Institut Européen des Membranes (UMR 5635) Spécialité : Chimie et Physicochimie des Matériaux Présentée par Aijing LU Copolymères à blocs amphiphiles et thermosensibles à base d'hydroxypropyl méthyl cellulose comme nano-vecteurs de principes actifs hydrophobes Amphiphilic and thermoresponsive block copolymers based on hydroxypropyl methyl cellulose as nano-carrier of hydrophobic drugs Soutenue le 2 avril, 2020 devant le jury composé de M. André DERATANI, DR, IEM UMR 5635 Invité M. Christophe MINGOTAUD, DR, IMRCP UMR 5623 Rapporteur M. Luc PICTON, Prof., PBS, UMR 6270 Rapporteur M. Mihai BARBOIU, DR, IEM UMR 5635 Président du jury M.
    [Show full text]
  • US5407445.Pdf
    ||||||||||||||||| USOO5407445A United States Patent (19) 11 Patent Number: 5,407,445 Tautvydas et al. 45 Date of Patent: Apr. 18, 1995 54 GEL COMPOSITION FOR IMPLANT 4,790,848 12/1988 Cronin . PROSTHESIS AND METHOD OF USE 4,795,463 1/1989 Gerow . 4,820,302 4/1989 Woodroof. 75 Inventors: Daiva K. Tautvydas, Atlanta; 4,820,303 4/1989 Brauman . Mannarsamy Balasubramanian, 4,822,741 4/1989 Bares . Roswell; R. Martin Emanuele, 4,828,561 5/1989 Woodroff. Alpharetta, all of Ga. 4,839,280 6/1989 Bares . 73 Assignee: Cytrk Corporation, Norcross, Ga. s: $3. kistan. 21 Appl. No.: 64,519 4,912,141 3/1990 Kronman , 4,936,858 6/1990 O'Keeffe . 22 Filed: May 19, 1993 4,955,909 9/1990 Ersek et al. 4,963,150 10/1990 Brauman . Related U.S. Application Data 4,995,882 2/1991. Destouet et al. a 5,019, 100 5/1991 Hennink et al. (63) in part of Ser. No. 886,264, May 20, 5,067,965 11/1991 Ersek et al. s 5,120,816 6/1992 Gould et al. 51) Int. Cl. ................................................ A61F 2/12 52 U.S. C. .......................................... 623/8; 623/11; OTHER PUBLICATIONS 623/66 Touchette, N., “Research. In Focus-Silicone Implants 58 Field of Search ............... 623/11, 16, 66; 528/76; and Autoimmune Disease: Studies Fail to Gel, The 424/422 Journal of NIH Research, vol. 4, pp.49-52 (May 1992). Gladwell, M., “FDA Wii Allow Limited Use of 56 References Cited Silicone-Gel Breast Implants', the Washington Post, U.S.
    [Show full text]
  • A Thesis Entitled the Preparation and Characterization of Poloxamer
    A Thesis entitled The Preparation and Characterization of Poloxamer-Based Temperature-Sensitive Hydrogels for Topical Drug Delivery. By Sarath Chandra Reddy Gandra Submitted to the Graduate Faculty as partial fulfillment of the requirements for The Master of Science Degree in Pharmaceutical Sciences with Industrial Pharmacy option Jerry Nesamony, Ph.D., Committee Chair Kenneth Alexander, Ph.D., Committee Member Sai Hanuman Sagar Boddu, Ph.D., Committee Member Dr. Patricia Komuniecki, Ph.D., Dean College of Graduate Studies The University of Toledo August 2013 Copyright © 2013 This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Preparation and Characterization of Poloxamer-Based Temperature-Sensitive Hydrogels for Topical Drug Delivery. by Sarath Chandra Reddy Gandra Submitted to Graduate Faculty as partial fulfillment of the requirements for The Master of Science Degree in Pharmaceutical Sciences with Industrial Pharmacy option The University of Toledo August 2103 Stimuli-sensitive hydrogels change their swelling behavior and drug release by sensing changes in the surrounding environment. One example is temperature-sensitive hydrogels which change their swelling behavior in response to a change in the environmental temperature. Poloxamers are tri-block copolymers that exhibit thermoreversible properties by transforming from a liquid-like behavior to gel-like behavior above a certain temperature called sol-gel transition temperature. By varying the concentration of poloxamer and other excipients, hydrogels with sol-gel transition point close to body temperature can be achieved. The aim of the present study was to develop poloxamer hydrogels as in situ gelling formulation for topical drug delivery.
    [Show full text]
  • Enhancement of the Rate of Solution of Relatively Insoluble Drugs from Solid-Solid Systems Prepared by Supercritical Fluid Technology
    ENHANCEMENT OF THE RATE OF SOLUTION OF RELATIVELY INSOLUBLE DRUGS FROM SOLID-SOLID SYSTEMS PREPARED BY SUPERCRITICAL FLUID TECHNOLOGY DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Carmen H. Ramirez, M.S. * * * * * The Ohio State University 2007 Dissertation Committee: Approved by Professor Sylvan G. Frank, Advisor Professor William L. Hayton Professor James T. Dalton ________________________ Advisor Professor Robert W. Curley Graduate Program in Pharmacy Copyright by Carmen H. Ramirez 2007 ABSTRACT Supercritical fluid technology, specifically the method of rapid expansion of supercritical solutions (RESS), has been used to prepare small particles consisting of solid solutions of a relatively insoluble drug and a water-soluble excipient. With an increasing number of relatively insoluble compounds being discovered, a general process for enhancing drug dissolution rates would assist formulation of these compounds for therapeutic use. Solid solutions could serve as a means for enhancing drug dissolution rates, since the drug is dispersed in a solid solvent in its smallest form, i.e., a molecule, prior to entering into solution. Therefore, solid solutions consisting of the relatively insoluble model drugs lidocaine or probucol and a water-soluble surfactant, poloxamers 407, 188, or 403 were prepared by RESS processing. Dissolution studies of these systems were performed and evaluated for their ability to enhance drug release rates. Furthermore, the mechanism by which solid solutions form in these systems was determined using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) was also used to study the surface characteristics of these particulate systems.
    [Show full text]
  • Large Triglyceride-Rich Lipoproteins in Hypertriglyceridemia Are Associated
    Zhang et al. Cell Death and Disease (2019) 10:728 https://doi.org/10.1038/s41419-019-1969-3 Cell Death & Disease ARTICLE Open Access Large triglyceride-rich lipoproteins in hypertriglyceridemia are associated with the severity of acute pancreatitis in experimental mice Yue Zhang1, Wenhua He1, Cong He1,JianhuaWan1, Xiao Lin2,3, Xi Zheng1,LeiLi1,XueyangLi1,XiaoyuYang1, Bingjun Yu1, Xunde Xian2,3, Yin Zhu1,YuhuiWang2,3,GeorgeLiu2,3 and Nonghua Lu1 Abstract Hypertriglyceridemia severity is linked to acute pancreatitis prognosis, but it remains unknown why a portion of severe hypertriglyceridemia patients do not develop severe acute pancreatitis. To investigate whether hypertriglyceridemia subtypes affect acute pancreatitis progression, we analyzed two genetically modified hypertriglyceridemia mouse models—namely, glycosylphosphatidylinositol high-density lipoprotein binding protein 1 knockout (Gpihbp1−/−) and apolipoprotein C3 transgenic (ApoC3-tg) mice. Acute pancreatitis was induced by 10 intraperitoneal caerulein injections. Biochemical assays and pathological analysis were performed for the severity evaluation of acute pancreatitis. Plasma triglyceride-rich lipoproteins (TRLs), including chylomicrons and very low-density lipoprotein (VLDL), were collected via ultracentrifugation to evaluate their cytotoxic effects on primary pancreatic acinar cells (PACs). We found that the particle sizes of Gpihbp1−/− TRLs were larger than ApoC3-tg TRLs. Severe pancreatic injury with large areas of pancreatic necrosis in the entire lobule was induced in Gpihbp1−/− mice when plasma triglyceride levels were greater than 2000 mg/dL. However, ApoC3-tg mice with the same triglyceride levels did not 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; develop large areas of pancreatic necrosis, even upon the administration of poloxamer 407 to further increase triglyceride levels. Meanwhile, in the acute pancreatitis model, free fatty acids (FFAs) in the pancreas of Gpihbp1−/− mice were greater than in ApoC3-tg mice.
    [Show full text]