Novel electrospun nanofibers incorporating polymeric prodrugs of ketoprofen: Preparation,characterization, and in vitro sustained release

A facile and efficient protocol for the preparation of nanofibers incorporating polymeric ketoprofen prodrugs and polyvinylpyrrolidone was developed. Polymeric ketoprofen prodrugs were constructed by a two‐step chemo‐enzymatic synthetic route, and nanofibers prepared by electrospinning from dimethylformamide/ethanol (1 : 1, v/v) solutions. The morphological characteristics of the fibers were influenced by the concentration of active agent in the spinning solution; average diameters varied from 196 to 370 nm. In vitro release studies indicated that the ketoprofen release rate from the electrospun fibers was significantly higher than that from the pure polymeric prodrugs. Cumulative drug release from the electrospun fibers reached 40–70% after 3 h and 75–100% after 12 h, while the pure polymeric prodrug released only 7–9% of the active agent over 12 h. Functional nanofibers incorporating polymeric prodrugs therefore comprise potentially effective drug delivery systems for sustained release. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1570–1577, 2013     

Multifunctional ternary drug‐loaded electrospun scaffolds

Multifunctional electrospun scaffolds were prepared from two polylactide (PLA) grades having slightly different d ‐lactide content (4.2 wt % and 2.0 wt %). Triclosan (TCS), ketoprofen (KTP), and p‐coumaric acid (CUM) were selected as bactericide, anti‐inflammatory, and antioxidant agents, respectively. Single, binary, and ternary drug‐loaded microfibers having a unimodal diameter distribution could be prepared using a common chloroform:acetone:dimethylsulfoxide mixture and similar operational parameters (i.e., voltage, flow rate, and tip–collector distance). FTIR spectra were sensitive to the low amount of drugs loaded and even showed slight differences in PLA conformation. DSC heating scans clearly demonstrated the ability of electrospinning to induce molecular orientation of PLA and also the nucleation effect of incorporated drugs to induce crystallization. Thus, crystallinity of binary drug‐loaded scaffolds was significantly higher than observed for unloaded samples. Release behavior of the three drugs from loaded scaffolds and PLA matrices in PBS:ethanol medium was evaluated. A rapid release was always detected, together with partial drug retention which was higher when the more stereoregular PLA matrix was employed. A strong bactericidal effect was found when scaffolds were loaded with 3 wt/vol % of TCS, but incorporation of a small percentage of KTP (i.e., 1 wt/vol %) had a bacteriostatic effect even in the absence of TCS. The inherent cytotoxicity of TCS could be well neutralized by enhancing cell viability by incorporation of CUM and/or KTP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42751.     

Preparation and performance evaluation of tetracycline hydrochloride loaded wound dressing mats based on electrospun nanofibrous poly(lactic acid)/poly(ϵ‐caprolactone) blends

In this article, we present the drug‐release rate, water uptake, water permeability, morphology, and mechanical properties of a series of active wound dressing nanofibrous mats prepared via an electrospinning process of poly(lactic acid) (PLA), poly(?‐caprolactone) (PCL), and their (50/50) blends loaded with different doses of tetracycline hydrochloride antibiotic. The performance of these active wound dressings in terms of a sustained and suitable drug‐release rate, adequate water uptake and water permeability, and antibacterial activities were compared with those of a commercial wound dressing (Comfeel Plus). The results show that the dressings made from PCL and PLA/PCL blends showed better performance compared with the commercial wound dressing sample as far as these properties were concerned. The improved performance could be explained on the basis of the nanofibrous structure of the mats and the hydrophilicity of PCL and PLA. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation of zinc-coordinated-DPA functionalized polyesters for gene condensation

Cationic polyesters have been widely utilized as efficient gene delivery carriers. Their ability in binding genes was majorly based on the electrostatic effect between the positive charges of polymers and the negatives charges of genes. It has been well known that large numbers of positive charges on the polymers would lead to undesired toxicity although strong gene binding capability. It was of great interest to developed a polymer with reduced positive charges while enhanced gene condensation ability. In this work, a library of polyesters functionalized by zinc-coordinated-dimethylpyridinium amine (DPA-Zn) have been successfully prepared by the polycondensation method starting from dimethyl 1,3-acetonedicarboxylate and 10 diols, followed by the post-modification using dimethylpyridinium amine and zinc nitrate. The post-modification efficiency was systemically evaluated and the optimized functionalization efficiency could reach around 50%. The gene condensation ability of the targeting polymers was also evaluated using gel retardation assay and dynamic light scatting. The results indicated that DPA-Zn functionalized polyesters could bind gene into nanocomplexes with the sizes around 200 nm.     

Dual drug release from CO2‐infused nanofibers via hydrophobic and hydrophilic interactions

This study investigated the effects of hydrophobic–hydrophilic interactions on dual drug release from CO₂‐infused nanofibers scaffolds (PCL, PCL–gelatin, and PCL “core” PCL–gelatin “shell”) using BODIPY 493/503 and Rhodamine B fluorescent dyes as drug models. Favorable dye–scaffold interactions increased total dye loading and promoted steady, more linear release. Unfavorable dye–scaffold interactions reduced overall loading and led to a greater burst release of dye. However, when CO₂ was used to infuse dye into an unfavorable scaffold, the changes in loading and release were less pronounced. When two dyes were infused, these behaviors were accentuated due to interactions between the dissolved forms of the dyes. Core–shell composite nanofibers displayed radically different release properties versus pure PCL–gelatin fibers when treated with dyes via CO₂ infusion. Dye release from core–shell scaffolds was highly sensitive to both interactions with scaffolds and the phase of CO₂ used to infuse the compounds of interest. By using different phases of CO₂ to partition dyes into hydrophobic and hydrophilic sections of core–shell nanofibers, such interactions can be manipulated to develop a bimodal drug release system with potential application in drug delivery or tissue engineering. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42571.     

Impacts of PEGylation on the gene and oligonucleotide delivery system

Poly(ethylene glycol) (PEG) is the most widely used polymer and also the gold standard in the field of drug delivery. Therapeutic oligonucleotides, for example, are modified with PEG at the terminus to increases nuclease resistance and the circulating half‐lives. The surface of nanoparticle such as micelle and liposome has been also modified with PEG. At present, one PEGylated therapeutic oligonucleotide has been approved for the market and several more PEGylated products including oligonucleotide and liposome are being tested in clinical settings. This review summarizes the methods and effects of PEGylation on gene delivery. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40293.     

Preparation and in vitro drug‐release behavior of 5‐fluorouracil‐loaded poly(hydroxybutyrate‐co‐hydroxyhexanoate) nanoparticles and microparticles

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) copolymeric microparticles (MPs) and nanoparticles (NPs) were prepared by the double‐emulsion solvent‐evaporation technique. 5‐Fluorouracil (5‐Fu), an anticancer drug, was entrapped in PHBHHx NPs and MPs. A variety of parameters, including the species and concentration of different surfactants, power and time of ultrasonication for particle dispersion, and organic/aqueous solution ratio, that affected the production of the 5‐Fu‐loaded PHBHHx NP and MP particles and the release of 5‐Fu were studied. The results show that the prepared NPs and MPs were spherical in shape and about 160 nm and 3 μm in size, respectively, when cetyltrimethyl ammonium bromide was used as the emulsifier. The drug‐loading content (DLC) varied from 3.53 to 8.03% for 5‐Fu‐loaded NPs and from 4.83 to 18.87% for 5‐Fu‐loaded MPs and depended on the different initial feeding amounts of 5‐Fu. The encapsulation efficiency decreased with increasing DLC. The in vitro drug‐release characteristics appeared to have two phases with an initial burst effect occurring within the first 8 h; this was more obvious for the particles with low DLCs. The NPs with high DLC (8.03%) had the slowest release rate, 49.6% of 5‐Fu within 24 h. Therefore, PHBHHx copolymeric NPs and MPs can possibly be applied as drug‐delivery carrier materials in the future. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Incorporation of chloramphenicol and captopril into poly(GL)‐b‐poly(GL‐co‐TMC‐co‐CL)‐b‐poly(GL) monofilar surgical sutures

Incorporation of chloramphenicol and captopril into coated and uncoated monofilament sutures was evaluated, as well as the derived bactericide and wound healing effects. To this end, a commercially available suture and an amorphous random copolymer constituted by trimethylene carbonate and lactide units were considered. The suture had a segmented architecture based on polyglycolide hard blocks and a soft block constituted by glycolide, trimethylene carbonate and ε‐caprolactone units. Chloramphenicol was better loaded when the coating copolymer was employed due to its protective effect whereas captopril showed an opposite behavior due to partial solubilization during immersion in the coating bath. Interestingly, the release behavior was very different for the two studied drugs since a significant retention of chloramphenicol was always detected, suggesting the establishment of interactions between drug and copolymers. On the other hand, delivery of captopril showed a typical dose dependent behavior. A low in vitro toxicity of the two drugs was determined considering both epithelial‐like and fibroblast‐like cells. Bactericide effect of chloramphenicol against Gram‐negative and Gram‐positive bacteria was demonstrated at a dose that was non‐toxic for all assayed cells. An accelerating wound healing effect of captopril was also demonstrated for early events. In this case, the use of a coating copolymer was fundamental to avoid cytotoxic effects on highly loaded sutures. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44762.     

Synthesis and characterization of a new amphiphilic copolymer containing multihydroxyl segments for drug carrier

A new amphiphilic copolymer (copoly‐(MR‐BMA‐HEA‐MAA), PRBHM) containing multihydroxyl segments was designed and synthesized for application in drug carrier. PRBHM can be dissolved in water to form aggregates directly with a critical aggregate concentration (CAC) of 0.0138 mg mL^?1. The chains of PRBHM can be collapsed into hydrophobic globules when pH decreases from neutral to slightly acid condition (pH = 5.0–7.0) in water. Since the hydrophilic hydroxyl group is independent on pH, PRBHM can keep stable both in neutral and slightly acid aqueous solutions. The hydrophobic small molecules such as 5‐(4‐(4‐vinylbenzyloxy) phenyl)‐4,5‐dihydro‐1,3‐diphenyl‐1H‐pyrazole (PY) can be loaded into PRBHM aggregates via ultrasonic treatment in water, and can be internalized into BEL‐7402 cancer cells. The cytotoxicity determination also indicates the good biocompatibility of PRBHM in potential application as a drug carrier. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Investigations on porous PLA composite scaffolds with amphiphilic block PLA‐b‐PEG to enhance the carrying property for hydrophilic drugs of excess dose

To address concern of the dispersion property of hydrophilic drugs of excess dose loaded in a hydrophobic poly(lactic acid) (PLA) matrix, this work developed a PLA and PLA‐b‐polyethylene glycol (PEG) composite scaffold ( ) and studied its carrier properties for aspirin as a model hydrophilic drug. The porous functional scaffolds were prepared from PLA and PLA‐b‐PEG solutions with the dose of 5, 10, and 15 wt % aspirin preloaded. The products and control samples of pure PLA with the same loading amount for comparison were characterized by scanning electron microscopy and X‐ray diffraction to examine the miscibility and porous structure. Rapid degradations in a strongly basic solution were performed to determine the actual loading amount and the encapsulation ratio. The in vitro release in phosphate buffer saline (PBS) at 37.5 °C indicated that the addition of amphiphilic block polymer may efficiently enhance the dispersion property and stabilize the release of hydrophilic drugs, especially with a high loading dose. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44489.     

Synthesis and evaluation of hyaluronic acid hydrogels modified with various crosslinkers as biodegradable polymers

Hyaluronic acid (HA), a high‐molecular‐weight natural polysaccharide, is often used in medical devices for regenerative medicine as it can undergo biodegradation via enzymatic action in the human body. HA exhibits both viscoelasticity and high biocompatibility and has therefore been used for ocular surgery. In particular, HA‐based hydrogels have been utilized as cell scaffold materials and devices in ophthalmological treatments. In this study, four hydrogels have been synthesized from HA derivatives with methacrylate groups and modified with crosslinkers such as adipic acid dihydrazide, divinyl sulfone, and dithiothreitol. Each of the synthesized hydrogels exhibits high transparency and strength as well as biodegradability in vitro. Hence, these HA‐based hydrogels demonstrate potential for applications as drug delivery systems and implants. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45453.     

Preparation and characterization of poly(vinyl alcohol) nanofiber mats crosslinked with blocked isocyanate prepolymer

Poly(vinyl alcohol) (PVA) nanofibers crosslinked with blocked isocyanate prepolymer (BIP) were successfully prepared using the electrospinning process and subsequent thermal treatment. Fourier transform infrared spectroscopy and solid‐state ¹³C NMR spectroscopy demonstrated that chemical crosslinks between the hydroxyl group of PVA and the isocyanate group of BIP were formed. Thermogravimetric analysis and differential scanning calorimetry results indicated that when the BIP content was increased, the thermal stability of PVA/BIP nanofibers increased, and the crystallinity of PVA decreased. Field emission scanning electron microscopy was used to measure the average diameter (200–300 nm) of the electrospun PVA/BIP nanofibers. The water contact angles were 10.2° and 113° for the pristine PVA nanofibers and PVA nanofibers crosslinked with 8 wt% BIP, respectively. The tensile strength of the crosslinked PVA nanofibers was 53.7 MPa, which was seven times higher than that of pristine PVA. The improved tensile strength and water resistance of the crosslinked PVA/BIP nanofibers were due to a combination of increased crosslinking density and decrease in the number of hydroxyl groups on the surface of the PVA/BIP nanofibers. Copyright © 2010 Society of Chemical Industry     

Sustained release of CIP from TiO2-PVDF/starch nanocomposite mats with potential application in wound dressing

Electrospinning is an economical and alluring method to fabricate wound dressing mats from a variety of natural and synthetic materials. In this study, polyvinylidene fluoride (PVDF) and starch composite mats containing ciprofloxacin (CIP) loaded on titanium dioxide nanoparticles (TiO₂) were prepared. Fourier Transform Infrared spectra of CIP, synthesized TiO₂ NPs, TiO₂/CIP, and PVDF/starch composite mats are analyzed. Scanning electron microscopy images revealed that the fiber diameter of PVDF nanofibers thickens by increasing starch, which varies between 180 nm and 550 nm. Strain at break of PVDF, starch, PVDF/starch (2:1 w:w; P2S1), PVDF/starch (1:1 w:w; P1S1), PVDF/starch (1:2 w:w; P1S2), and nanofibers were 103 ± 11, 3 ± 0.6, 27 ± 4, 52 ± 5.2, 7.7 ± 1%, respectively. Based on strain at break and young modulus, P2S1 was selected as a suitable candidate for wound dressing to which load TiO₂/CIP as a bioactive agent. The release rate of CIP showed that about 40% of the drug is released in the first 2 days. Furthermore, the antibacterial activity of dressings was investigated using Escherichia coli and Staphylococcus aureus microorganisms and zones of clearance were obvious around the specimen on the agar plate. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48916.     

Development of tunable biodegradable polyhydroxyalkanoates microspheres for controlled delivery of tetracycline for treating periodontal disease

This article was aimed at preparation and characterization of drug delivery carriers made from biodegradable polyhydroxyalkanoates (PHAs) for slow release of tetracycline (TC) for periodontal treatment. Four PHA variants; polyhydroxybutyrate (PHB), poly(hydroxybutyrate‐co‐hydroxyvalerate) with 5, 12, and 50% hydroxyvalerate were used to formulate TC‐loaded PHA microspheres by double emulsion‐solvent evaporation method. We also compared the effect of different molecular weight (M_w) of polyvinyl alcohol (PVA) acting as surface stabilizer on particle size, drug loading, encapsulation efficiency, and drug release profile. The TC‐loaded PHA microspheres exhibited microscale and nanoscale spherical morphology under scanning electron microscopy. Among formulations, TC‐loaded PHB:low M_w PVA demonstrated the highest TC loading with slow release behavior. Our results showed that the release rate from PHA microspheres was influenced by both the type of PHA and M_w of PVA stabilizer. Lastly, TC‐loaded PHB microspheres showed efficient killing activity against periodontitis‐causing bacteria, suggesting its potential application for treating periodontal disease. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44128.     

Hydrophobically graded polyester polyol acrylate polymers: Synthesis,characterization, and microencapsulation of sulfamethoxazole for controlled release application

Polyester polyol macromers were prepared by using diacid‐diol condensation reaction using succinic acid as the acid component and polyethylene glycol 200 (PEG 200) as the diol component. Replacing PEG 200 with increasing amounts of butanediol resulted in macromers, which upon acrylation of end hydroxy groups and polymerization resulted in polymers with graded hydrophobicity depending on the amount of butanediol present in the polymer. These polymers showed expected trends in water equilibrium swells, equilibrium water contact angles, and in vitro degradation times depending on the amount of modification with butanediol. These polymers were used to microencapsulate sulfamethoxazole as a model drug and the in vitro delivery of the drug also followed the expected trend depending on the polymer hydrophobicity. Thus, it was shown that it is possible to prepare polyesters of graded properties by judicious selection of diacids and diols. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4058–4065, 2006     

Design and characterization of pH stimuli-responsive nanofiber drug delivery system: The promising targeted carriers for tumor therapy

New carrier platforms have been designed for an electrospun pyridinium calixarene nanofiber for controlled drug delivery. First, 5,11,17,23-tetra-tert-butyl-25,27-bis(3-aminomethyl-pyridineamido)-26,28-dihydroxycalix[4]arene (3-AMP) scaffold was produced by electrospinning. AMP scaffold was modified by human serum albumin (HSA), folic acid (FA), and glutathione (GSH). Doxorubicin (DOX) was loaded to surfaces of the AMP, AMP-HSA, AMP-HSA-FA, and AMP-HSA-GSH nanofibers by using DOX solution in different buffers with, 2.2, 4.0, 6.0, and 7.4 pH. The release studies DOX from four different nanofibers was also done in a various amount microenviroments by changing pH values. The loading and release amount of DOX was estimated from the calibration curve drawn at 480 and 560 nm of excitation and emission wavelengths by using a fluorescence spectrophotometer. The loading studies were confirmed by Fourier transforms infrared, atomic force microscopy, transmission electron microscopy, scanning electron microscope, and energy-dispersive X-ray (EDX) analysis.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

Hemocompatibility of polymers for use in vascular endoluminal implants

Implanted polymers for cardiovascular applications may function as structural supports, barriers, or provide a means for local drug delivery. Several thermoplastic biodegradable drug delivery polymers are potential candidates for blood-contacting implant applications. For intravascular applications specifically, a criterion for material selection is the intrinsic hemocompatibility of the baseline polymer. As an initial screening approach for selection of polymers for in vivo use, thin films of polyesters: poly(ɛ-caprolactone) (PCL), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA); polyanhydrides: poly(fatty acid dimer-co-sebacic acid) (PFAD:SA) and poly(biscarboxyphenoxypropane-co-sebacic acid) (PCPP:SA); and poly(ethylene glycol) (PEG)-ylated polyesters: PLA:PEG, PCL:PEG and PCL:PLA:PEG polymers were spin-cast on glass cover slips and placed in an in vitro flow system exposing them at a controlled shear to overflowing human whole blood. Platelet adherence, aggregate formation, and thrombus formation, as well as leukocyte adherence were assessed following 5 min of flow. At 5 min of flow the rank order of materials, in terms of least to most thrombogenic was: PCL < PFAD:SA < PCPP:SA < PLGA < PLA. All PEGylated materials, in general, had less thrombus formation than baseline unmodified materials.     

Preparation and drug‐release behavior of minocycline‐loaded poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] films

In this work, biocompatible hydrogel matrices for wound‐dressing materials and controlled drug‐release systems were prepared from poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] [p(HEMA‐co‐PEG–MA] films via UV‐initiated photopolymerization. The characterization of the hydrogels was conducted with swelling experiments, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (differential scanning calorimetry), and contact‐angle studies. The water absorbency of the hydrogel films significantly changed with the change of the medium pH from 4.0 to 7.4. The thermal stability of the copolymer was lowered by an increase in the ratio of poly(ethylene glycol) (PEG) to methacrylate (MA) in the film structure. Contact‐angle measurements on the surface of the p(HEMA‐co‐PEG–MA) films demonstrated that the copolymer gave rise to a significant hydrophilic surface in comparison with the homopolymer of 2‐hydroxyethyl methacrylate (HEMA). The blood protein adsorption was significantly reduced on the surface of the copolymer hydrogels in comparison with the control homopolymer of HEMA. Model antibiotic (i.e., minocycline) release experiments were performed in physiological buffer saline solutions with a continuous flow release system. The amount of minocycline release was shown to be dependent on the HEMA/PEG–MA ratio. The hydrogels have good antifouling properties and therefore are suitable candidates for wound dressing and other tissue engineering applications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation of bioactive glycosylated glial cell‐line derived neurotrophic factor‐loaded microspheres for medical applications

Poly (lactic‐co‐glycolic acid) (PLGA)‐coated gelatin microspheres containing glial cell‐line derived neurotrophic factor (GDNF) were developed by thermal gelation through a water‐in‐oil emulsion technique. Gelatin types (A and B) at four different pH levels were investigated for their influences on the morphology, the microsphere size, the zeta potential, and the swelling ability. The encapsulation of GDNF and the release characteristics of GDNF were also determined using enzyme‐linked immunosorbent assay (ELISA). The maximum cumulative released amounts of GDNF from the microspheres were increased from 50 to 90% after 4 d (based on the actual amount of the GDNF). Thus, the release of the GDNF contents in the microspheres depends on the amount of GDNF. Trigeminal ganglion cells (TGCs) were used to study the bioactivity of GDNF released from the microspheres, which was proven to retain its bioactivity in promoting the TGCs' neurite outgrowth. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40167.