Study On Preparation And Drug Controlled Release Behaviour Of Poly(Ethylene Glycol)/Polyanhydride Block Copolymers

A series of copolymers of polyethylene glycol and polyanhydrades: P(SA-OA), mPEG-b-PSA-b-mPEG, mPEG-b-POA-b-mPEG, mPEG-b-P(SA-DLLA)-b-mPEG, mPEG-b-P(SA-RA)-b-mPEG, and mPEG-b-P(OA-DLLA)-b- mPEG were prepared via melt-polycondensation from sebacic acid(SA), octadecanoic diacid(OA), ricinoleic acid(RA), D,L-lactic acid (DLLA) and polyethylene glycol monomethylether(mPEG). The structure of the copolymers was characterized by FT-IR, 1H-NMR, DSC and XRD. The results indicate that the copolymers were obtained with designed structure. The introduction of RA and DLLA into the polyanhydride moieties weakens the crystallinity of polyanhydride obviously.In vitro hydrolytic degradation and in vitro drug release behaviors of P(SA-OA) were investigated. The results show that the degradation rate of P(SA-OA) is decreased with the content of OA increasing and P(SA-OA) can control the release of the entrapped drug salicylic acid and paclitaxel.The drug loaded nanoparticles of mPEG-b-P(SA-RA)-b-mPEG, mPEG-b-POA-b-mPEG and mPEG-b-P(OA-DLLA)-b- mPEG were prepared via nano-precipitate technique. The diameter of the nanoparticles are about 200 nm measured by Laser Particle Analyzer and TEM. The diameter of the nanoparticles is decrease with the crystallinity of anhydride linkages reducing, while increase with increasing the proportion of the hydrophobic segments and the solid content in the solution. The nanoparticles also present good performance on drug controlled release of paclitaxel. The release rate increases with reducing the crystallinity of anhydride linkages or increasing the drug loaded amount, and also is decreased by increasing the proportion of the hydrophobic segments.It was found that the aqueous solution of mPEG-b-POA-b-mPEG can undergo"gel-sol"transition with temperature changing, while those of mPEG-b-P(SA-DLLA)-b-mPEG and mPEG-b-P(OA-LA)-b-mPEG can undergo"sol-gel-sol"transition. As the concentration of polymer and the proportion of the hydrophobic segments increase, the"sol-gel"transition temperature decreases, while the temperature of"gel-sol"transition increases. In vitro drug release behaviors of these three hydrogel systems were studied respectively with 5-fluorouracil, paclitaxel and bovine serum albumin(BSA) as model drugs. The results illustrate that the hydrogel of mPEG-b-P(SA-DLLA)-b-mPEG can release 5-fluorouracil at a constant release rate in the former 32 h and the cumulative release amount up to 63.4%. The hydrogels of mPEG-b-POA-b-mPEG and mPEG-b-P(OA-LA)-b-mPEG also have apparent drug controlled release behaviour by using paclitaxel and BSA as model drugs. Their release behaviors are basically in accord with zero-order release and the release rate decrease with increasing the proportion of the hydrophobic segments.The in vivo retention experiments were conducted by subcutaneously injecting polymers solution into the rats. Hydrogel was formed as soon and the retention time was between 5 days and 20days. The results of cytotoxicity experiments indicate that mPEG- b-POA-b-mPEG and mPEG-b-P(OA-DLLA)-b-mPEG have no cytotoxicity to cells.