Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60 µm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5 µg VEGF (V5) and 50 µg VEGF (V50) per 500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.

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Multiblock terpolymer of poly(L-lactic acid)/poly(ethylene oxide)/poly(L-aspartic acid), (PLLA/PEO/PAsp) was synthesized by ring opening polymerization of beta -benzyl L-aspartate N-carboxyanhydride, Asp(OBzl)-NCA with alpha-omega -hydroxy terminated triblock PLLA/PEO/PLLA copolymer. The resulting multiblock terpolymer was characterized by several techniques including Fourier transform infrared spectroscopy and differential scanning calorimetry.(1)H nuclear magnetic resonance spectra indicated the molar ratio of PLLA/PEO/PAsp (OBzl) to be 86/10/4. Thermal gravimetric analysis and environmental scanning electron microscopy data showed that PLLA/PEO/PAsp had crystalline and brittle structure. In order to improve its mechanical and physical properties, the terpolymer was blended with high molecular weight poly(L-lactic-co-glycolic acid) copolymer, PLGA(85/15) (M(w): 95000 gmol(-1)) in 25/75 and 50/50 mole ratios. The hydrolytical degradation properties of these polymers were studied. Degradation experiments were performed during a 48-day period in pH:7.4 phosphate-buffered saline (PBS) at 37 degrees C. The observed molecular weight losses were 91% and 67% for the 25/75 and 50/50 mixtures, respectively. In vitro attachment and growth of L929 mouse fibroblasts on these biopolymers were also investigated. Cell growth experiments indicated that the copolymer blend allowed the attachment and growth of cells.

Poly(lactic acid)/poly(glycolic acid)/poly(dimethylsiloxane) (PLGA/TEGOMER) terpolymers have been synthesized by the ring-opening polymerization of L-lactide and glycolide with alpha,omega-amine-terminated poly(dimethylsiloxane) prepolymer, using stannous octoate as a catalyst. The resulting terpolymers were characterized by various analytical techniques including size exclusion chromatography, 1H-nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy, and differential scanning calorimetry. The data showed that the terpolymers presented an amorphous structure. The glass transition temperature decreased with increasing TEGOMER unit content. For in vitro degradation studies, porous films were fabricated using a solvent-casting, particulate leaching technique. Degradation of the PLGA/TEGOMER terpolymer was studied in phosphate-buffered saline at pH 7.4 and 37 degrees C. The degradation was followed by intrinsic viscosity, mass loss, and molecular weight measurements, and 1H-NMR spectroscopy. The mass loss after 55 days was 76% for the PLGA/TEGOMER (71/24/5) sample. Cell growth experiments using Swiss 3T3 fibroblasts demonstrated that PLGA/TEGOMER terpolymer matrices allow the attachment and growth of cells.