Preparation And Characterization Of Chitosan/PHB-PEG Block Copolymer Micro-Nanoparticles

Chitosan (CS) is a kind of widespread basic polysaccharide in the biosphere. CS has already been widely used as the biological material in the field of food, pharmaceutical, oral drug delivery and drug carriers because of the biocompatibility, biodegradability and non-toxicity. Poly (β-butyrolactone) (PHB) is a natural polymer produced by the microorganism under unbalanced growth conditions. It can be extracted from microorganisms, and can also be synthesized by various chemical methods. PHB is mainly applied in the field of drug delivery and tissue engineering because of the excellent biocompatibility and biodegradability. Polyethylene glycol (PEG) or polyethylene glycol methyl ether (mPEG) has a wide range of applications in biomedical field because of its hydrophilic and biocompatible. But these three substances also have some drawbacks. CS has low water solubility and poor biocompatibility at body pH environment. PHB can not be effectively applied at body water environment because of its hydrophobic. A series of modification was carried to meet our needs.In the study, PHB was synthesized with naphthalene potassium-crown ethers as initiator. The relationship between molecular weight of PHB and time was studied. There is the linear relationship between the molecular weight and time in the range of 0.5hours and 9.5hours. PEG-potassium macro initiators or mP EG-potassium macro initiators were synthesized based on naphthalene potassium-crown ethers initiators. PHB-PEG-PHB and mPEG-PHB were prepared by anionic ring-opening polymerization of β-butyrolactone (BL) with macro initiators. Copolymers were characterized by FTIR, NMR, GPC, DSC. The nanoparticles of copolymers were characterized by SEM, TEM, DLS.CS/PHB-PEG-PHB and CS-g-PHB-mPEG were prepared by the coupling effect of 1,6-hexamethylene diisocyanate (HDI). These were characterized by FTIR and TG to study structure and thermal stability. The hydrophilic segments (mPEG or PEG) and hydrophobic segments (PHB) were grafted on chitosan chain by graft modification.Finally, the chitosan based micro-nanoparticles were prepared through macromolecular self-assembly technology of amphiphilic polymer. The morphology and size of micro-nanoparticles were characterized by SEM and DLS. It was found that the morphology and size of chitosan-g-PHB-mPEG based copolymer micro-nanoparticles were better for drug carriers. Reducing the initial concentration of the copolymer, reducing the final concentration of micro-nanoparticles, dialysis and ultrasonic oscillation were benefical to prepare micro-nanoparticles used in drug carriers. Morphology and size of the copolymer CS-g-PHB-mPEG micro-nanoparticles prepared by the direct dialysis method are relatively good. The size of micro-nanoparticles is about 100 nm. But the adhesion phenomenon of micro-nanoparticles is obvious.