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

摘要

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 GI_(50) (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.