Drug-loading of poly(ethylene glycol methyl ether methacrylate) (PEGMEMA)-based micelles and mechanisms of uptake in colon carcinoma cells

In this study polymeric micelles formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(methyl methacrylate)(P(PEGMEMA(75))-b-PMMA(80)) block copolymer of approximately 25 nm in diameter were used to encapsulate the model drug, Nile Red, with a loading efficiency of 0.08 wt% and a chemotherapeutic drug, doxorubicin (DOX), with an efficiency of 2.75 wt%. The release of DOX from the micelles was sufficient to be cytotoxic to human colon carcinoma cells, WiDr, while Nile Red and the unloaded micelles were found not to be cytotoxic when exposed to the cells at polymer concentrations up to 200 mu g/mL. Nile Red loaded micelles were used to analyze uptake of the micelles into the cells which were rapidly internalized within minutes of exposure. The three major endocytotic pathways were involved in the internalization of micelles; however other passive mechanisms were also at play as the addition of inhibitors to all three pathways did not completely inhibit the uptake of these nanoparticles. These data demonstrate the potential of the P(PEGMEMA)(75)-b-PMMA(80) block copolymer micelles to be rapidly internalized by carcinoma cells and deliver low doses of drugs intracellularly for controlled drug release. Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved.