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Blend Electrospinning, Coaxial Electrospinning, and Emulsion 11 Electrospinning Techniques

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Blend Electrospinning, Coaxial Electrospinning, and Emulsion 11 Electrospinning Techniques Blend electrospinning, coaxial electrospinning, and emulsion 11 electrospinning techniques Matej Buzgo1, Andrea Mickova1, Michala Rampichova2 and Miroslav Doupnik1 1InoCure s.r.o., Klimentska´ 1652/36, 110 00 Prague, Czech Republic, 2Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i, Vı´denskaˇ ´ 1083,142 20, Prague 4, Czech Republic 11.1 Advanced electrospinning techniques Electrospinning is a recent fiber-forming technology enabling production of fibrous scaffolds for use in tissue engineering [1,2], biomedicine [3,4], filtration [5]¸ and other technical applications [6,7]. The process is based on drawing of fibers from polymeric solution or melt using high electrostatic forces. Apparatus for electro- spinning uses high-voltage power supplies to generate potential up to 50 kV. Upon effect of electrostatic forces, the polymeric solution is attracted towards the oppo- site electrode and a straight jet of solution is formed from a conical protrusion, often called a Taylor cone, leading to fibers with diameter in submicron range [8]. Classical electrospinning process is used for the formation of porous matrices, which was reviewed in numerous publications [1,2,9,10]. The key properties of fibrous meshes are high porosity, very high surface-to-volume ratio, high pore inter- connectivity, and thin fiber diameter [1,2]. The morphology of fibrous layer is mim- icking the structure of extracellular matrix and facilitates application of electrospun scaffolds is in the field of tissue engineering and nanomedicine. Besides medical field, the structure of electrospun fibrous meshes has advantageous properties for application in liquid and air filtration [5]. Apart from classical electrospinning tech- niques, advanced electrospinning techniques attracted huge attention due to possi- bility to prepare multimaterial and drug functionalized materials. This chapter focuses on properties and use of these advanced methods and strategies. 11.2 Nanofibers as a drug delivery system The ability to regulated drug delivery is changing the way of how drugs are admin- istrated to patients. In classical dosage formulation, the drugs are delivered alone or Core-Shell Nanostructures for Drug Delivery and Theranostics. DOI: https://doi.org/10.1016/B978-0-08-102198-9.00011-9 © 2018 Elsevier Ltd. All rights reserved. 326 Core-Shell Nanostructures for Drug Delivery and Theranostics in combination with excipients in single doses. They have rapid bioavailability but also rapid clearance times. This dosage mode is ideal for drugs with desired rapid action (i.e., antiinflammatory drugs, pain reducing drugs, antibiotics); however, for long-term and chronic application, they are associated with the need for periodic dosage intervals. Drug delivery systems prolong this time and enable more conve- nient dosage to patients. Nevertheless, combination with drug delivery system enables elimination of drug degradation (i.e., first pass metabolism in liver), elimi- nate systemic effect of drugs (i.e., toxicity of cytostatics), and target drug release to desired areas (i.e., tumor delivery) [11,12]. Electrospun nanofibers present numerous advantages for their use as drug deliv- ery systems [1,9]. Due to their enormous specific surface area, they enable adsorp- tion of drugs and simple functionalization. In addition, the encapsulated drugs are efficiently released from bulk matrix of fibers through the high surface depending on diffusion/degradation mechanisms. The process enables regulation of release depending on fiber chemical and morphological composition [13]. Due to pore interconnectivity and high porosity, the drugs could freely diffuse from the mesh after release. The scaffold structure in the form of fibrous mesh facilitates the use of advanced nanofibers as topical or implantable depot release devices. In contrary to nano and microparticles, the nanofibrous systems are less suited for injection delivery and release in systemic circulation. However, the combination of biomi- micking surface and drug release properties allows utilization of such systems in tissue engineering (i.e., implants and scaffolds) [14 18], as patches (i.e., skin deliv- ery, buccal delivery, implantable hernia, or cardiac patches) [19 21] and dressings (i.e., wound dressings) [19,21]. Electrospun scaffolds could be functionalized by numerous methods. Drugs can either be attached superficially to the nanofiber surface or internalized (encapsu- lated) into the nanofiber core. Drug adsorption is the simplest method. The loading amount and adsorption/desorption rate is dependent on surface properties of fibers and finding optimal composition is often problematic. Drug encapsulation aims to diminish this major shortcoming. There are several ways to encapsulate drugs into the nanofiber matrix by electrospinning. The most common methods include blend electrospinning, emulsion electrospinning, and coaxial electrospinning. 11.3 Functionalization of nanofibers by surface adsorption Physical adsorption to the nanofiber surface is a simple way to functionalize nanofi- bers for drug delivery. The large specific surface of nanofibers means that they can be loaded with a high amount of drugs. However, the adsorbed molecules are often released too rapidly and the systems are more suitable for short-term drug delivery. The adsorption/desorption ratio is regulated by surface properties of electrospun fibers. For instance, cationic exchange surface was developed using sulfonated polystyrene fibers [22]. The fibers were used for binding of five cationic drugs Blend electrospinning, coaxial electrospinning, and emulsion electrospinning techniques 327 (dextromethorphan, chlorpheniramine, diphenhydramine, propranolol, and salbuta- mol). The drug adsorption/desorption behavior correlated with drug properties (pKa, lipophilicity, molecule size, and steric properties) and solvent properties (con- centration and valence of ions in releasing solution). The salbutamol was released with the fastest rate (order of minutes) due to its lowest molecular weight, lowest hydrophobicity (low hydrophobic interactions), and lower affinity of cationic groups to sulfonylated surface. With the increase of these parameters, the desorp- tion rate was slower (order of hours). The results illustrate the need of complex optimization of numerous parameters to find proper balance between drug adsorp- tion/desorption rate and optimal delivery time interval for molecules bound on the surface of fibers. Electrospun fibers were combined with a range of drugs by surface adsorption (i.e., tetracycline, ciprofloxacin, and bisphenol) [23,24]. In addition, proteins were also loaded on the surface of fibers. However, susceptible molecules are not protected from environmental degradation and their bioactivity is lowered. Nie et al. [25] showed that immobilization of BMP-2 to the surface of nanofibers resulted in 75% release during the first 5 days. Similarly, other growth factors, such as epidermal growth factors (EGF) [26], basic fibroblast growth factor (bFGF) [27], nerve growth factor (NGF), and ciliary neurotrophic factor [28], were bound on the surface of fibers. To increase the loading capacity of proteins, specific motives have been imple- mented to the surface of fibers. Lam et al. [27]. prepared EGF and bFGF functiona- lized fibers by coating of fiber surface by heparin. The factors interacted with heparin moieties and helped in improving of axon growth on scaffolds. Similarly, PVA fibers with phosphatidylcholine on surface enabled enhanced adsorption of insulin and stim- ulation of cartilage defect restoration on model of minipig [29]. Nevertheless, the nanofibers could also be further functionalized by surface- bound drug delivery systems. Nanofibers, due to their enormous surface, are serving as a platform for binding of such systems, enable localization of drug release to desired areas of scaffolds, and provide spatial localization on site of implantation. The surface of fibers was modified by binding liposomes as delivery system for proteins. Rampichova et al. [30] adsorbed liposomes with encapsulate fetal bovine serum for stimulation of chondrocyte proliferation. Similar system was utilized for release of gentamicin from liposomes [31]. Nevertheless, other membrane systems were used as drug delivery systems. Among them, Vocetkova et al. [32] and Jakubova et al. [33] used polycaprolactone (PCL) nanofibers as a scaffold for adhe- sion of human platelets. Platelets serve as natural source of growth factors and stim- ulated fibroblasts, keratinocytes, melanocytes, and chondrocytes. Nanofibers were combined also with nano/microparticles particles for the development of composite systems [34]. For instance, nanofibers were coated with silica nanoparticles contain- ing ibuprofen [35]. Coating by adsorptive polymer (polydopamine) facilitates improved adhesion of nanoparticles and enables further regulation of additional drugs encapsulated in fibers (i.e., doxorubicin). Such multistage release systems have potential in medication of complex diseases. Protein-loaded microspheres were electrosprayed on poly(lactic-co-glycolic acid) (PLGA) fibers to prepare drug releasing scaffolds [36,37]. The system enabled to prepare diverse density of 328 Core-Shell Nanostructures for Drug Delivery and Theranostics electrosprayed particles resulting in the formation of gradient of released biomole- cules (BMP-2). Bock et al. [38] prepared protein releasing composite by combining electrospinning
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