Study Of Sustained Release Of Poly(?-caprolactone)-Poly(ethylene Glycol) And Poly(?-Caprolactone/Glycolide)-poly(ethylene Glycol) Block Copolymer Micelles

In recent years,biodegradable aliphatic polyesters such as polylactide?PLA?,polycaprolactone?PCL?and polyglycolide?PGA?have become the research hotspots of biodegradable materials due to their excellent biocompatibility.In biomedical fields,they are widely used as surgical sutures,drug controlled release carriers and tissue engineering scaffolds.These polyesters can be degraded into small molecules by hydrolysis and then absorbed by the body.However,strong hydrophobicity,semi-crystalline properties and lacking of functional groups restrict their further applications.Through introducing hydrophilic components such as polyethylene glycol?PEG?,the polymer chain structure can be modified,thus adjusting the physicochemical properties of the polyester to meet diverse needs in the biomedical field.In this paper,a series of poly??-caprolactone?–poly?ethylene glycol??PCL-PEG?and poly??-caprolactone/glycolide?–poly?ethylene glycol?[P?CL/GA?-PEG]diblock copolymers with various molecule weights were synthesised by ring-opening polymerization of?-caprolactone or a mixture of ?-caprolactone and glycolide using monomethoxy PEG?mPEG?as macroinitiator and stannous octanate[Sn?Oct?₂]as catalyst.The composition,molecular weight,crystalline structure and thermomal properties of the copolymer were studied by ¹H NMR,GPC,DSC and WXRD.Copolymer micelles were prepared by using the co-solvent evaporation method.Morphology and size of the micelles were observed by TEM and DLS and the critical micellar concentration?CMC?was determined by pyrene fluorescence probe spectroscopy.Drug-loaded micelles were prepared by solvent evaporation method,using paclitaxel as model drug.The drug encapsulation efficiency?EE?,loading content?LC?and drug release behavior were determined by HPLC.Hemocompatibility and cytocompatibility were determined to evaluate the biocompatibility of the block copolymer micelles.In vitro degradation experiments were conducted to investigate the degradation behavior of the PCL-PEG block copolymer micelles.The results show that PCL-PEG and P?CL/GA?-PEG diblock copolymers have very low CMC values which ensure the stability of micelles after administration in the body and dilution in blood.The drug-loaded micelles obtained by the solvent evaporation method have high EE and LC.Paclitaxel released proceeded slowly and steadily within a month.Block copolymer micelles present good biocompatibility and show potential as drug delivery carriers.The PCL-PEG block copolymer micellar degradation behavior can be explained by a two-stage degradation mechanism:interfacial erosion between the core and the shell firstly,followed by core erosion.