Star Block Polycaprolactone Biodegradable Unimolecular Micelles for Drug Delivery

Abstract

Unimolecular micelles, a class of nanoparticles that are resistant to concentration gradient, are critically required for drug delivery due to the plethora of benefits they offer over conventional aggregated micelles. Star polymers have proved to be the major players towards formation of these unimolecular micelles owing to the ease of synthesis and density of their core. The present investigation is to probe the ability of fully biodegradable polycaprolactone (PCL) star polymers to self-assemble into unimolecular micelles as their arm numbers are increased keeping the arm length constant throughout. Multifunctional initiators were exploited for ring opening polymerization of ε-caprolactone and γ-tert butyl substituted caprolactone to construct star block copolymers in a solvent-free melt process. The thermal properties of the PCL macroinitiators revealed that their packing efficiencies decreased with increase in branching while upon addition of the second block became completely amorphous. Higher arm number and higher degree of branching retarded inter-polymer interaction and facilitated the formation of unimolecular micelles as opposed to the formation of conventional multi-micellar aggregates in lower arm number polymers. The dense cores of these unimolecular micelles enabled them to load high amounts of the anticancer drug doxorubicin (DOX ~12-15 %) compared to the aggregated micelles (~3-4 %). The star unimolecular micelle completely degraded leading to 90% release of the loaded drug upon treatment with esterase enzyme in vitro. The anticancer efficacies of these DOX loaded micelles were tested in breast cancer cell lines (MCF 7) and their IC50 values were found to be much lower compared to that of aggregated micelles. Time-dependent cellular uptake of aggregated micelles saturated after 3 h whereas the uptake of unimolecular micelles kept increasing till 12 h as determined from confocal image-based quantification. The present work provides a systematic study on the advantages of biodegradable unimolecular micelles as the next generation nano delivery platform that promises to circumvent the shortcomings of conventional multi-molecular micelles.