Cyclodextrin Modified Biodegradable Polyester And Its Drug Control Release System

Due to their excellent biodegradability,biocompatibility and bioabsorbance, poly-ε-caprolactone(PCL) and polylactide(PLA) are widely used in biomedical fields.In order to improve their properties it is usually used to synthesize their block or random copolymer by adjust the molar ratio of the two monomers.Another method usually be used to modify their properties is introducing branch structure into the polymer chain.First,block copolymer of poly-ε-caprolactone-b-lactide with 85 to 15 mole ratio (CL:LA) was synthesized and the biodegradation behavior as implant were investigated in vitro and in vivo.The biodegradation behaviors of in vitro and in vivo were similar.PLA segment was degraded initially because it was amorphous so its mole ratio was decreased in the beginning period of degradation.The crystallinity and fusion enthalpy of the implant were increased in the process of degradation.The appearance form of the implants was also sustained after three years and the weight loss is only about 25%(in vivo),so the polymer maybe used for long-acting drug delivery system.Cyclodextrin is a kind of cyclic polysaccharides with special structure and properties,and it is also extensively used as drug carrier.By using its hydrophilicity property and multi-hydroxy in the molecules,it is possible to introduce hydrophilicity and branched structure to PCL or PLA to enhance their degradation rates.Using anionic ring-opening polymerization method,PCL withβ-cyclodextrin (β-CD)as the end functional group were synthesized and characterized.Some polymerization factors influence on the monomer conversion and molecular weight and distribution,such as the mole ratio of monomer and initiator,polymerization temperature and polymerization time were investigated.Polymerization with high monomer conversion and narrow polymer molecular weight distribution was obtained at 60～70℃and 8 hours reaction.Because of containingβ-CD unit at the end of PCL chain,the water uptake was enhanced and contact angle was decreased,so the hyrophilicity of PCL was improved.Star-shaped PCL,PDLLA and PLLA based onβ-CD as the core were also synthesized by using anionic ring-opening polymerization and characterized.The reactive conditions that controlled the number of the star-shaped polymer arms and the influence of number of arms on the polymer properties were evaluated.The number of anionic hydroxyl ofβ-CD determined not only the arms,but also the polymerization rate and the monomer conversion,the more the number of anionic hydroxyl ofβ-CD,the more the arms of the star-shaped polymer and the faster the polymerization rate with higher monomer conversion.Star-shaped polymer has lower melting temperature,crystallbility,intrinsic viscosity than linear polymer at the similar molecular weight.The chiral difference of DLLA and LLA had no effect on the ring-opening polymerization results.As model protein,by using W/O/W solvent evaporation method,bovine serum albumin(BSA) was encapsulated in linear PCL and star-shaped PCL microspheres. The degradation behavior and BSA release behavior were studied.It was obviously that the degradation rate of star-shaped polymer was faster than the linear polymer at the similar molecular weight,and the more the arms,the faster the degradation rate. Microspheres prepared from star-shaped PCL showed higher drug-loading amount, small burst effect and fast release rate compared to those prepared from linear PCL.