Thermosensitive in situ hydrogel of paclitaxel conjugated poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)
2012
This paper aimed at engineering a multifunctional drug delivery system to provide efficient drug loading and sustained and site-specific drug release for prolonged formulation. Paclitaxel conjugated poly(e-caprolactone)-poly(ethylene glycol)-poly(e-caprolactone)(PCEC/PTX) was synthesized by conjugating paclitxel(PTX) to carboxylic acid-terminated poly(e-caprolactone)-b-poly(ethylene glycol)-b-poly(e-caprolactone)(PCEC). PCEC/PTX could self-assemble into nanoparticles (NPs) with high PTX content (20%, w/w) in the cores. The PCEC/PTX NPs performed pH sensitive drug release and presented a similar anticancer efficacy as PTX. Significantly, the aqueous solution of PCEC/PTX NPs freeze-dried powder presented a thermosensitive reversible sol-to-gel transition property around body temperature, which provided a possibility of injectable site-specific administration. Not only free PTX but also PTX-loaded NPs could be released from PCEC/PTX hydrogel. The in vitrocell uptake results of Rhodamine B conjugated PCEC NPs indicated the PCEC/PTX NPs could be endocytosized by cancer cells efficiently. The in vivo gel degradation studies showed that PCEC/PTX hydrogel could sustain at least 28 days after subcutaneous injection. These results suggested PCEC/PTX hydrogel could be employed as an injectable anti-cancer drug for site-specific administration to achieve the sustained release of PTX.
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