Synthesis And Characterization Of Amphiphilic Star Block Copolymers Based On PEO And PCL

Amphiphilic copolymers are of particular interest because their microstructure possess both hydrophobic and hydrophilic properties and can form a versatile micellar structure in selective solvents. The hydrophobic segment of the polymer forms the core of the micelles, whereas the hydrophilic segment forms the corona or outer shell. This core-shell structure could be used as a drug delivery system, and hydrophobic drugs are loaded in the hydrophobic core. To this goal, different types of drug carriers have been designed. The most widely studied amphiphilic polymers for drug delivery include diblock copolymers and triblock copolymers. However, the conventional micelle drug delivery systems based on the linear amphiphilic copolymers suffer from low encapsulation efficiency and fast initial release rate, which limit their applications in drug delivery. In this article, we designed and synthesised two kinds of amphiphilic star-shaped copolymers.Among the investigated amphiphilic copolymers, the most utilized hydrophilic component is Poly(ethylene oxide)(PEO). PEO is a typically hydrophilic block, a significant amount of water molecules can be bound onto its backbone via H-bonding. An important aspect of the PEO is nontoxic, biodegradable and biocompatible, which could meet the biocompatibility demand excellently when incorporating synthetic materials into biological system. With a PEO-based shell, the microparticles formed can avoid the adsorption of proteins and adhesion of cells in biological media. The most utilized hydrophobic component is poly (ε-caprolactone) (PCL), it has also been widely used as important drug delivery carriers because of its biocompatibility and biodegradability.In this article, several well-defined star copolymersβ-CD-PCL21-PEO21 and PEO4-PCL4 with different PEO segment molecular weight and different PCL segment molecular weight were successfully prepared by the combination of living anionic polymerization(AROP) and coordination ring-opening polymerization(CROP). The main results summarized as follows:1. Amphiphilic star-shaped copolymersβ-CD-PCL21-PEO21 of predictable molecular weights and narrow polydispersities were successfully synthesised by CROP and AROP, as shown by 1H NMR and GPC.The amphiphilic star block copolymer is capable of self-assembling into sphere micelles in water, we observed the morphology of the micelles with Electronic Transmission Electron Microscop (TEM). The critical micellar concentration (CMC) was found to decrease with the increasing of hydrophobic segment molecular weight, and increase with the increasing of hydrophilic segment molecular weight. Resulted polymeric micelles loaded with indomethacin showed a much improved drug release behavior due to the special micellar structure.2. In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive PEO4-PCL4 hydrogel was studied. The prepared PEO4-PCL4 hydrogel undergoes temperature-dependent sol-gel transition, which is a flowing sol at ambient temperature and turns into a non-flowing gel at around physiological body temperature. The in vitro release behavior of hydrophilic small-molecule drug indomethacin from PEO4-PCL4 hydrogel were also investigated in detail. The results showed that the model drugs could be released from the PEO4-PCL4 hydrogel system over a sustained period. Therefore, PEO4-PCL4 hydrogel is promising for use as an injectable local drug delivery system.