Sustained release of mitomycin-C from poly(DL-lactide)/poly(DL-lactide-co-glycolide) films

Mitomycin-C (MMC)-loaded poly(DL-lactide) (PLA)/poly(DL-lactideco-glycolide) (PLGA) films which have different drug loading capacities and thicknesses were prepared by a solvent-evaporation technique. Degradation and release studies were conducted at 37°C in pH 7.4 phosphate buffered saline. The results showed that both the rate and the percentage of released MMC increased as the glycolide content in the copolymer increased from 10 to 30% (w/w) and the drug load increased from 0.5 to 2 mg MMC per 300 mg of polymer. In contrast, they decreased depending upon increasing film thickness from 80 to 300 μm and polymer molecular weight. It was found that the drug release mechanism is diffusion-controlled according to a non-Fickian diffusion mechanism.     

Microstructure and drug-release studies of sirolimus-containing poly(lactide-co-glycolide) films

Sirolimus-containing poly(lactide-co-glycolide) (PLGA) films were prepared by solution casting and removing the residual solvent, 1,4-dioxane, by liquid and supercritical carbon dioxide (CO(2) ) extraction. The effect of lactide:glycolide ratio, stereochemistry of PLGA, and extraction condition (i.e., temperature and pressure) on the polymer and drug morphologies was studied using wide-angle X-ray scattering and differential scanning calorimetry. The polymer and drug crystallinity increased after liquid and supercritical CO(2) extraction, and the level of drug crystallinity within the film depended on the extraction conditions. Generally, higher levels of drug crystallinity were observed in the films with amorphous polymer matrices, and the drug crystallinity increased with temperature and pressure of the extraction conditions. In vitro drug elution from these films was studied using a USP 4 apparatus. Polymer crystallinity was found to be the determining factor for drug release, whereby films with higher polymer crystallinity eluted less drug compared to films with amorphous polymer matrices.     

Degradation behaviour in vitro for poly(D,L-lactide-co-glycolide) as drug carrier

Biodegradable polymers have been extensively investigated because of regulating drug release rate easily, obviating the need to remove the device, and good biocompatibility. Among the biodegradable polymers currently under investigation, poly(D,L-lactide-co-glycolide) (PLGA) copolymers are the most widely studied because of their long history of safe clinical use as drug carrier. 50 : 50 PLGA was used as a model degradable polymer in this study to investigate the degradation behaviour on drug release from bulk degradable polymers in vitro. 5-fluorouracil (5-FU) was used as a model drug. Molecular weight change, residual mass, water uptake, morphological change of PLGA wafers, and pH of release test medium were characterized to investigate the effect of polymer degradation on drug release. The release rate of 5-FU increased with the increase of 5-FU loading amount and the release profiles of 5-FU irrespective of 5-FU loading amount followed near first order release kinetics.     

A novel hemostatic delivery device for thrombin: biodegradable poly(D,L-lactide-co-glycolide) 50:50 microspheres

Topical thrombins are locally active hemostatic agents that can be used to minimize blood loss during any surgery. The aim of this study was to design and investigate a thrombin-containing biodegradable hemostyptic device with an optimized drug release profile to promote local blood clot formation. It is effective with ongoing systemic antithrombotic therapy and can be used in all types of bone-related surgery, for example, in dental surgery. Thrombin-loaded poly(D,L-lactide-co-glycolide) microspheres were synthesized by means of complex (w/o/w) emulsion evaporation method. The resulting enzyme activity of the serine-protease thrombin was verified by the specific chromogenic substrate S-2238. The thrombin release profile depended on four factors: (1) thrombin dosage, (2) polymer concentration in the o-phase, (3) phase quotient w1:0 in the primary emulsion, and (4) the addition of pore-introducing agents. A collagenous sponge containing thrombin-loaded microspheres by means of lyophilization was developed. The impact of several production factors of the (w1/o/w2) solvent evaporation method to optimize thrombin encapsulation, morphology of the spheres, and desired drug release profile have been investigated. The in vitro thrombin release was dependent on the polymer-to-oil phase ratio, the polymer concentration, and the type of solvent and polymer. The porosity of the spheres and release rate of the active agent were enhanced by increasing the inner aqueous w1 phase. With this study, a new biodegradable hemostyptic device could be verified and established for a potentially safe and locally controlled thrombin release to manage postsurgical hemorrhage in patients undergoing anticoagulant therapy.     

Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels

Controlled drug release devices of pH-sensitive, complexing poly(acrylic acid-g-ethylene glycol) (P(AA-g-EG)) hydrogels were prepared by free radical solution UV polymerization. The effects of hydrogel composition, polymerization conditions and surrounding environment on theophylline release kinetics and drug transport mechanisms were evaluated in these P(AA-g-EG) polymer networks. Release studies indicated a dependence of the theophylline release kinetics and diffusion coefficients on the hydrogel structure, polymerization conditions and pH of the environment. The theophylline transport mechanism was studied by fitting experimental data to five different model equations and calculating the corresponding parameters. The Akaike information criterion was also considered to elucidate the best-fit equation. Results indicated that in most release cases, the drug release mechanism was anomalous (non-Fickian). This indicates that such systems may, under certain conditions, provide release characteristics approaching zero-order release. The pH of the dissolution medium appeared to have a strong effect on the drug transport mechanism. At more basic pH values, Case II transport was observed, indicating a drug release mechanism highly influenced by macromolecular chain relaxation. The results obtained in this research work lead us to the conclusion that P(AA-g-EG) hydrogels can be successfully used as drug delivery systems. Their versatility to be designed with specifically tuned release properties renders these biomaterials promising pharmaceutical carriers for therapeutic agents.     

Synthesis,characterization and controlled drug release from temperature-responsive poly(ether-urethane) particles based on PEG-diisocyanates and aliphatic diols

A series of linear amphiphilic poly(ether-urethane)s with alternative hydrophilic/hydrophobic segments based on PEG-diisocyanates and aliphatic diols is developed. The molecular structures of the copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectra and gel permeation chromatography. Nanoparticles prepared by self-assembly of the resulting copolymers show sharp temperature-responsive phase transition. The phase transition temperature could be easily modulated by the length of hydrophilic or hydrophobic segments of the polymer. The mechanism of the temperature-responsive behaviour is discussed. In the presence of these obtained poly(ether-urethane)s, doxorubicin (DOX) could be dispersed into aqueous solution. The ratio of DOX release from polymeric particles increased sharply above the phase transition temperature, while the release was suppressed below the phase transition temperature. A controlled drug release can be achieved by changing the environmental temperature. The easy-prepared polymeric nanoparticles, with features of biocompatibility, biodegradability and tail-made temperature responsiveness, are a kind of promising carriers for temperature-controllable drug release.     

Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro

Transmucosal drug delivery (TMD) system using mucoadhesive polymer has been recently interested due to the rapid onset of action, high blood level, avoidance of the first-pass effect and the exposure of the drug to the gastrointestinal tract. A novel mucoadhesive polymer complex composed of chitosan and poly(acrylic acid) (PAA) was prepared by template polymerization of acrylic acid in the presence of chitosan for the TMD system. Triamcinolone acetonide (TAA) was loaded into the chitosan/PAA polymer complex film. TAA was evenly dispersed in chitosan, PAA polymer complex film without interaction with polymer complex. Release behavior of TAA from the mucoadhesive polymer film was dependent on time, pH, loading content of drug, and chitosan PAA ratio. The analysis of the drug release from the mucoadhesive film showed that TAA might be released from the chitosan/PAA polymer complex film through non-Fickian diffusion mechanism.     

Evaluation of in vitro drug release, pH change, and molecular weight degradation of poly(L-lactic acid) and poly(D,L-lactide-co-glycolide) fibers

Biodegradable fibers of poly(L-lactic acid) (PLLA) and poly(D,L-lactide-co-glycolide) (PLGA) that encapsulated a water-soluble drug were created by a patented technique consisting of wet-spinning a water-in-oil emulsion. These fibers are 2.4% by mass drug, which is slowly released, making these fibers potential candidates for implantation as drug delivery devices and/or tissue-engineering substrates. Drug release kinetics and changes in molecular weight were investigated over time. This study demonstrated that drug release rates and molecular weight degradation are a function of the amount of aqueous phase added as an emulsion during fabrication. The type of polymer used (PLLA or PLGA) determines the molecular weight degradation rates, but has little effect on drug release kinetics.     

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.     

Biodegradable drug carriers based on poly(ethylene glycol) block copolymers

The synthesis of a model water-soluble drug carrier system based on poly(ethylene glycol) (PEG) block copolymers is described. In the system, two blocks of PEG are connected via a biodegradable oligopeptide or amino acid linkage incorporating at least one glutamic acid residue. A drug model (4-nitroaniline) is attached to the γ-carboxyl group of glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. All oligopeptides were prepared as potential substrates for cathepsin B, a representative of lysosomal enzymes. The relationship between the structure of oligopeptides forming the linkage between two PEG molecules and the rate of cathepsin B-catalyzed polymer chain degradation is evaluated. The relationship between the structure of the spacer and kinetics of drug model release from the carrier after incubation in cathepsin B solution is also discussed in detail. The results show that, by altering the structure of oligopeptides in the polymer construct, marked changes in the rate of both polymer degradation and the drug model release can be achieved.     

Efficacy of antibiotics-loaded interpenetrating network (IPNs) hydrogel based on poly(acrylic acid) and gelatin for treatment of experimental osteomyelitis: in vivo study

The safety and efficacy of gentamycin sulphate (GS)- or vancomycin hydrochloride (VCl)-loaded polymer devices based on poly(acrylic acid) and gelatin crosslinked selectively using 0.3 mol % N,N'-methylene bisacrylamide and 1 wt% glutaraldehyde were evaluated by varying the drug concentration onto the devices. The placebo and drug-loaded device of AxGx (acrylic acid:gelatin: 1:1 w/w) were employed for the treatment of experimental osteomyelitis in rabbit. Rabbits were categorized into four groups. Twelve rabbits in each group were treated with 12+/-1 mg of AxGx-1a (22% w/w GS), 12+/-1 mg of AxGx-1b (44% w/w GS), 16+/-1 mg of AxGx-1b (44% w/w GS) and 16+/-1 mg of AxGx-1c (44% w/w VCl). The drug concentration was measured following implantation in the adjacent tissue of femoral cavity, and serum. In femoral cavity maximum drug concentration was found on the 7th day with all the four types of devices. No drug was found after 21 days, at the local site with devices AxGx-1a and AxGx-1b (12+/-1 mg), whereas it was detected after 6 weeks with 16+/-1 mg device (44% w/w GS or VCl). Macroscopic evaluation after treatment revealed that swelling, redness, local warmth and drainage decreased depending upon the drug loading of the implants. Sequential radiographs, histology, microbiologic assay and scanning electron micrography demonstrated devices AxGx-1b and AxGx-1c (16+/-1 mg of 44% w/w drug loading) to be the most suitable device, which heals the infection after 6 weeks of treatment. No significant difference (p>0.05) in the rate of healing was observed between GS- and VCl-loaded devices. None of the implant showed toxic level of drug in serum at any given time.     

Sustained drug release characteristics of biodegradable composite poly(d,l)lactic acid-poly(l)lactic acid microcapsules containing ciprofloxacin

Ciprofloxacin polylactic microcapsules were prepared by the phase separation process. Two types of polylactic acid, poly(d,l)lactic acid and poly(l)lactic acid were combined as membrane materials to prevent the aggregation which happened frequently in the phase separation process. The polymer compositions of the microcapsules can influence the release rate of Ciprofloxacin. The optimal release rate of the drug can be obtained by modifying microcapsule compositions. Poly(d,l)lactic acid is superior in slowing the rate of drug release than poly(l)lactic acid. However, poly(l)lactic acid is necessary in the preparation of the microcapsules to prevent aggregation.     

Silk fibroin/poly(vinyl alcohol) photocrosslinked hydrogels for delivery of macromolecular drugs

Hydrogels are three-dimensional polymer networks widely used in biomedical applications as drug delivery and tissue engineered scaffolds to effectively repair or replace damaged tissue. In this paper we demonstrate a newly synthesized cytocompatible and drug releasing photo-crosslinked hydrogel based on poly(vinyl alcohol) methacrylate and silk fibroin which possesses tailorable structural and biological properties. The initial silk fibroin content was 0%, 10%, 20%, 30%, 40% and 50% with respect to the weight of poly(vinyl alcohol) methacrylate. The prepared hydrogels were characterized with respect to morphology, crystallinity, stability, swelling, mass loss and cytotoxicity. FITC-dextrans of different molecular weights were chosen as model drugs molecules for release studies from the hydrogels. The hydrogels containing different silk fibroin percentages showed differences in pore size and distribution. X-ray diffraction analysis revealed that amorphous silk fibroin in poly(vinyl alcohol) methacrylate is crystallized to β-sheet secondary structure upon gelation. The sol fraction increased with increasing fibroin concentration in the co-polymer gel (from 18% to 45%), although the hydrogel extracts were non-cytotoxic. Similarly, the addition of silk fibroin increased water uptake by the gels (from 7% to 21%). FITC-dextran release from the hydrogels was dependent on the silk fibroin content and the molecular weight of encapsulated molecules. The study outlines a newer type of photo-crosslinked interpenetrating polymer network hydrogel that possess immense potential in drug delivery applications.     

Preparation and characterization of poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel

Microspheres of a new kind of copolymer, poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA), are proposed in the present work for clinical administration of an antineoplastic drug paclitaxel with hypothesis that incorporation of a hydrophilic PEG segment within the hydrophobic PLA might facilitate the paclitaxel release. Paclitaxel-loaded PLA-PEG-PLA microspheres of various compositions were prepared by the solvent extraction/evaporation method. Characterization of the microspheres was then followed to examine the particle size and size distribution, the drug encapsulation efficiency, the colloidal stability, the surface chemistry, the surface and internal morphology, the drug physical state and its in vitro release behavior. The effects of polymer types, solvents and drug loading were investigated. It was found that in the microspheres the PEG segment was homogeneously distributed and caused porosity. Significantly faster release from PLA-PEG-PLA microspheres resulted in comparison with the PLGA counterpart. Incorporation of water-soluble solvent acetone in the organic solvent phase further increased the porosity of the PLA-PEG-PLA microspheres and facilitated the drug release. A total of 49.6% sustained release of paclitaxel within 1 month was achieved. Potentially, the presence of PEG on the surface of PLA-PEG-PLA microspheres could improve their biocompatibility. PLA-PEG-PLA microspheres could thus be promising for the clinical administration of highly hydrophobic antineoplastic drugs such as paclitaxel.     

Characterization of polymeric poly(epsilon-caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids

Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been encapsulated with poly(epsilon-caprolactone) (PCL) microspheres using a w / o /w double emulsion method. The microspheres prepared were smooth and spherical, with a mean size from 8-25 microm. In vitro release profiles of microspheres showed a trend of increasing initially at the first week, and thereafter the release was sustained. At the end of the seventh week LNG/EE from 1:5 and 1:10 PCL microspheres were 60 and 48%, 52 and 46%, respectively. An in vitro degradation study shows that at the 20th week the microspheres maintained the surface integrity. The PCL microspheres showed a triphasic in vivo release profile with an initial burst effect due to the release of the steroid adsorbed on the microsphere surface, a second sustained release phase due to the steroid diffusion through the pores or channels formed in the polymer matrix, and third phase due to polymer bioerodible. Histological examination of PCL microspheres injected intramuscularly into thigh muscle of a rat showed a minimal inflammatory reaction demonstrating that contraceptive steroid-loaded microspheres were biocompatible. The level of inflammatory cytokines determined by immunostaining for IL-1alpha, the tissue response to formulations at the first week was considered mild, whereas at the end of the 20th week the inflammatory response ceased. Thus, this study helped us to evaluate the feasibility of using these microspheres as a long-acting biodegradable drug delivery system for contraceptive steroids.     

Matrix Modifications Modulate Ophthalmic Drug Delivery From Photo-Cross-Linked Poly(propylene Fumarate)-Based Networks

In this work, different modifications of photo-cross-linked poly(propylene fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM) was increased by adding various amounts of poly(ethylene glycol) (PEG) or by increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior to cross-linking. The in vitro release studies that utilized high-performance liquid chromatography for quantification revealed highly accelerated drug release from the matrices with increasing contents of the hydrophilic modifier. AZ was released from matrices containing 5% PEG in 56 days, which equals approximately 25% of the release period found for the unmodified matrices. A comparable acceleration in drug release was found for TM-loaded samples modified with 5% PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM release duration by one-third. A significant acceleration in drug release was also found for the samples that were fabricated from a PPF–NVP mixture with increased NVP content. Matrix water content and erosion were assessed gravimetrically. Micro-computed tomography was used to image structural changes of the release systems and shed light on the drug-release mechanism. This study showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the drug release of two ophthalmic drugs and represent a suitable tool to adjust drug-release rates from PPF-based matrices for different therapeutic needs.     

Mechanistic evaluation of the glucose-induced reduction in initial burst release of octreotide acetate from poly(D,L-lactide-co-glycolide) microspheres

One major obstacle for development of injectable biodegradable microspheres for controlled peptide and protein delivery is the high initial burst of drug release occurring over the first day of incubation. We describe here the significant reduction in initial burst release of a highly water-soluble model peptide, octreotide acetate, from poly(D,L-lactide-co-glycolide) microspheres by the co-encapsulation of a small amount of glucose (e.g., 0.2%w/w), i.e., from 30+/-20% burst - glucose to 8+/-3% + glucose (mean+/-SD, n=4). This reduction is unexpected since hydrophilic additives are known to increase porosity of microspheres, causing an increase in permeability to mass transport and a higher burst. Using the double emulsion-solvent evaporation method of encapsulation, the effect of glucose on initial burst in an acetate buffer pH 4 was found to depend on polymer concentration, discontinuous phase/continuous phase ratio, and glucose content. Extensive characterization studies were performed on two microsphere batches, +/-0.2% glucose, to elucidate the mechanism of this effect. However, no significant difference was observed with respect to specific surface area, porosity, internal and external morphology and drug distribution. Continuous monitoring of the first 24-h release of octreotide acetate from these two batches disclosed that even though their starting release rates were close, the microspheres + glucose exhibited a much lower release rate between 0.2 and 24h compared to those - glucose. The microspheres + glucose showed a denser periphery and a reduced water uptake at the end of 24-h release, indicating decreased permeability. However, this effect at times was offset as glucose content was further increased to 1%, causing an increase in surface area and porosity. In summary, we conclude that the effect of glucose on initial burst are determined by two factors: (1) increased initial burst due to increased osmotic pressure during encapsulation and drug release, and (2) decreased initial burst due to decreased permeability of microspheres.     

In vitro release of clomipramine HCl and buprenorphine HCl from poly adipic anhydride (PAA) and poly trimethylene carbonate (PTMC) blends

Controlled drug-delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring-opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC-PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules.     

Changing the release kinetics of gentamicin from poly(D,L-lactide) implant coatings using only one polymer

Creating orthopedic implants that locally deliver drugs is an appealing approach to induce bone regeneration and prevent or treat infections. In this study, titanium K-wires were coated with poly(D,L-lactide) (PDLLA) solutions with different polymer/solvent/drug ratios to modify the release kinetics of the antibiotic gentamicin. The concentrations of PDLLA ranged from one-fold (100 mg/1.5 mL solvent, 1X) to four-fold (400 mg/1.5 mL solvent, 4X), where the higher concentrations led to the thickening of the drug-loaded coatings and an increase of total coating mass. Coated wires were incubated in PBS buffer at 37 °C for up to 32 weeks, and the elution kinetics were analyzed at several time points. Different release profiles were observed: I) a burst release within the first hours for the coatings made out of lower concentrations of PDLLA with higher amounts of gentamicin and II) a sustained release of up to 14 weeks for the different coatings with higher polymer amounts with lower concentrations of gentamicin. Moreover, the amounts of remaining gentamicin on the wires after elution were dependent on the coating composition. Nearly complete gentamicin was released from the 1X PDLLA coatings and approximately one-third with respect to initial gentamicin remained in the 4X coatings. Based on these results, we garnered a better understanding of the parameters that influenced release kinetics in this simple system and described how to realize different release patterns by using only one polymer. Using this knowledge, tailored coated implants that can improve infection prophylaxis or stimulate bone healing may be designed.     

Morphological and degradation studies of sirolimus-containing poly(lactide-co-glycolide) discs

The effect of residual solvent and copolymer ratio on the in vitro degradation and drug release behavior of a bioabsorbable polymer/drug system was investigated in an effort to understand and develop the use of these excipients for controlled drug delivery devices. Sirolimus-containing poly(lactide-co-glycolide) (PLGA) discs were fabricated by a solution-casting method using dimethyl sulfoxide (DMSO) as the solvent. The residual DMSO was removed from a set of discs by supercritical carbon dioxide extraction, and reflections of crystalline sirolimus were observed in the wide-angle X-ray scattering profile observed after extraction. A correlation was not observed between the extent of drug crystallization and extraction conditions and copolymer ratio. Mass loss, molecular weight, and sirolimus release were monitored during an in vitro study of the oven-dried neat PLGA, sirolimus-containing PLGA, and extracted sirolimus-containing PLGA discs during 56 days. The sirolimus-containing PLGA discs with residual DMSO exhibited a faster sirolimus release rate compared to the extracted discs. The residual DMSO facilitated release of sirolimus. The discs that contained PLGA with higher glycolide content, particularly 50% glycolide, degraded faster and exhibited faster sirolimus release.