Study on injectable paclitaxel loaded PCL/PEG/PCL thermosensitive hydrogels

Abstract

Objective To construct an injectable controlled delivery system of paclitaxel based on thermosensitive PCL1250-PEG1500-PCL1250 hydrogels. Methods A thermosensitive PCL1250-PEG1500-PCL1250 triblock copolymer was synthesized by ring-opening polymerization of e-CL using PEG (Mw=l 500) as the initiator and Sn(Oct)2 as the catalyst. The synthesized PCL1250-PEG1500-PCL1250 copolymers were characterized for their composition,structure, and molecular weight via 1H NMR and GPC techniques. A series of Paclitaxel loaded hydrogels with various predesigned hydrogel concentrations and initial drug loadings were prepared to investigate their gelation ability, in vitro drug release behavior and in vivo biodegradability. Results The results calculated from 1H NMR and GPC indicated that EG/CL ratio(1.55) was consistent with the initial feed ratio(1.6), which offered a strong proof to their composition and molecular structure. The thermosensitive PCL1250-PEG1500-PCL1250 hydrogels exhibited a desirable sol-gel transition ability within the concentration range of 15%-30%. The in vitro release rate of paclitaxel from the paclitaxel/PCL1250-PEG1500-PCL1250 hydrogels was controllable by altering the hydrogel concentrations and initial drug loadings. The PCL1250-PEG1500-PCL1250 hydrogels showed a good in situ gelation ability after subcutaneously injected into mouse back. The in situ formed hydrogels gradually degradated with time and almost disappeared after 45 days in vivo. Conclusion Both the controllable drug release behavior and promising biodegradability of this new thermosensitive PCL1250-PEG1500-PCL1250 hydrogels paved a way to develop a novel delivery system for paclitaxel. Key words: Thermosensitive hydrogels; PCL1250-PEG1500-PCL1250copolymers; Paclitaxel; Controlled release; Biodegradability