Curcumin-Loading-Dependent Stability of PEGMEMA-Based Micelles Affects Endocytosis and Exocytosis in Colon Carcinoma Cells.

Polymeric micelles were formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(PEGMEMA)-b-PS) block copolymer of two different chain lengths. The micelles formed were approximately 16 and 46 nm in diameter and used to encapsulate curcumin. Upon loading of the curcumin into the micelles, their size increased to approximately 34 and 80 nm in diameter, respectively, with a loading efficiency of 58%. The unloaded micelles were not cytotoxic to human colon carcinoma cells, whereas only the smaller loaded micelles were cytotoxic after 72 h of exposure. The micelles were rapidly internalized by the cells within minutes of exposure, with the loaded micelles internalized to a greater extent owing to their enhanced stability compared to that of the unloaded micelles. The larger micelles were more rapidly internalized and exocytosed than the smaller micelles, demonstrating the effect of micelle size and drug loading on drug delivery and cytotoxicity.

Profluorescent PPV-Based Micellar System as a Versatile Probe for Bioimaging and Drug Delivery.

Although micelles are commonly used for drug delivery purposes, their long-term fate is often unknown due to photobleaching of the fluorescent labels or the use of toxic materials. Here, we present a metal-free, nontoxic, nonbleaching, fluorescent micelle that can address these shortcomings. A simple, yet versatile, profluorescent micellar system, built from amphiphilic poly(p-phenylenevinylene) (PPV) block copolymers, for use in drug delivery applications is introduced. Polymer micelles made from PPV show excellent stability for up to 1 year and are successfully loaded with anticancer drugs (curcumin or doxorubicin) without requiring introduction of physical or chemical cross-links. The micelles are taken up efficiently by the cells, which triggers disassembly, releasing the encapsulated material. Disassembly of the micelles and drug release is conveniently monitored as fluorescence of the single polymer chains appear, which enables not only to monitor the release of the payload, but in principle also the fate of the polymer over longer periods of time.

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(PEGMEMA75)-b-PMMA80) block copolymer of approximately 25nm in diameter were used to encapsulate the model drug, Nile Red, with a loading efficiency of 0.08wt% and a chemotherapeutic drug, doxorubicin (DOX), with an efficiency of 2.75wt%. 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 200µg/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-PMMA80 block copolymer micelles to be rapidly internalized by carcinoma cells and deliver low doses of drugs intracellularly for controlled drug release.

Size effects of self-assembled block copolymer spherical micelles and vesicles on cellular uptake in human colon carcinoma cells.

Block copolymers, poly(oligo ethylene glycol methyl ether methacrylate)-block-poly(styrene), POEGMEMA-b-PS, with various block lengths were prepared via RAFT polymerization and subsequently self-assembled into various aggregates to investigate their uptake ability into human colon carcinoma cell lines, WiDr. By varying the ratio of the hydrophobic to hydrophilic block lengths in the block copolymers various morphologies including spherical micelles, cylindrical micelles (rods), vesicles and large compound micelles could be generated. With increasing length of the hydrophobic block the micelles grew in size until chain stretching caused the transition to rods and then to other aggregates. Micelles of two sizes with a hydrodynamic diameter of 34 and 49 nm, respectively, and two different vesicles (hydrodynamic diameters 99 nm and 150 nm) were further studied towards their ability to be taken up by human colon carcinoma cells. Results indicated that the smaller sized micelles were taken up almost immediately while an increased sized micelle was taken up, however at a slower rate. Though larger vesicle aggregates were taken up at a slower rate, eventually all cells internalized aggregates to a similar amount after a few hours.