Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone- co-caprolactone)- b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

具有不同疏水嵌段组成的聚(甲基己内酯-共-己内酯)-b-聚(环氧乙烷)共聚物的合成、自组装和药物输送特性:结合化学和微流体处理用于聚合物纳米药物

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作者:Zheqi Xu, Changhai Lu, Carly Lindenberger, Yimeng Cao, Jeremy E Wulff, Matthew G Moffitt

Abstract

The synthesis, characterization, and self-assembly of a series of biocompatible poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) amphiphilic block copolymers with variable MCL contents in the hydrophobic block are described. Self-assembly gives rise to polymeric nanoparticles (PNPs) with hydrophobic cores that decrease in crystallinity as the MCL content increases, and their morphologies and sizes show nonmonotonic trends with MCL content. PNPs loaded with the anticancer drug paclitaxel (PAX) give rise to in vitro PAX release rates and MCF-7 GI50 (50% growth inhibition concentration) values that decrease as the MCL content increases. We also show for selected copolymers that microfluidic manufacturing at a variable flow rate enables further control of PAX release rates and enhances MCF-7 antiproliferation potency. These results indicate that more effective and specific drug delivery PNPs are possible through tangential efforts combining polymer synthesis and microfluidic manufacturing.

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