Synthesis Of Amphiphilic Biodegradable Block Copolymers And Their Use As Drug Carriers

Nowadays,more and more attention has been paid for applying biodegradable polymers as a controlled drug release carrier.The pharmaceutical preparation from biodegradable materials could be degraded into low-molecular-weight metabolites, which will avoid the in vivo accumulation of the carrier materials.At the same time,the drug release rate could be controlled by modulating the degradation rate of carrier materials.In our study,a series of amphipathic biodegradable copolymers were synthesized,and characterized.Their drug delivery property on folic acid under different conditions was also investigated.Firstly,we used ring-opening polymerization and functional group coupling action to prepare cysteine modified amphiphilic block copolymer acetate-polylactide-block-poly (ethylene glycol)-Cysteine(APLA-b-PEG-Cys) copolymers.The structure and molecular weight were characterized by FT-IR,~1H-NMR and GPC.The polymer could self-assemble to form micelle with nano-size and regularly spherical in shape in aqueous solution.Folic acid(FA) was then used as a model drug to incorporate into APLA-b-PEG-Cys micelles.To enhance the stabilization of APLA-b-PEG-Cys micelle and control the drug release,the shell of APLA-b-PEG-Cys micelle was crosslinked by the in situ polycondensation of amino acid moieties on its surface.The effects of shell-crosslinking on the micelle physicalchemistry properties were investigated in detail.It was found that,the shell-crosslinking changed the surface potential,micelle size and model drug(FA) release behavior,but it did not significantly affected the micelle morphology and drug encapsulation efficiency of APLA-b-PEG-Cys micelles. These results suggest that the novel copolymer could be used in drug delivery systems.Secondly,amphiphilic biodegradable poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone)(PCEC) triblock copolymers have been successfully synthesized by the ring-opening polymerization ofε-caprolactone(ε-CL) employing SnOct as catalyst and double-hydroxyl capped PEG(DHPEG) as macro-initiator.The triblock structure and copolymer composition were conformed by FT-IR,~1H-NMR and GPC.Using a membrane dialysis method,PCEC micelles were prepared with a core-shell type.The critical micelle concentration(CMC) of PCEC triblock copolymers was determined by fluorescence technique using pyrene as probe,and CMC values decreased with the increase of PCL chain length.From the observation of transmission electron microscopy(TEM),the morphology of polymer micelles was spherical in shape.Micelles size measured by dynamic light scattering(DLS) exhibited a narrow size distribution.Folio acid(FA) was then used as a model drug to incorporate into PCEC micelles.The diameter,drug loading,and drug release rate of PCEC micelles were influenced by the feed weight ratio of FA and copolymer,and polymer composition.In addition,in vitro release experiments of the drug-loaded PCEC micelles exhibited sustained release behavior without any burst effects and the release behavior was also affected by the pH of release media.