The low bioavailability of poorly water-soluble therapeutic agents remains a critical aspect for clinical implementation. Drug encapsulation in carriers -particularly in polymer-based nanometer sized carriers- addresses some of these issues. While polymeric micelles have shown significant advantages over small-molecule analogs, they have also been reported to suffer from disruption or dissociation, largely attributed to dilution in the bloodstream. Strategies to address instability issues of polymeric micelles include covalent cross-linking of either core or corona compartments, yet another approach to by-pass micellar dissociation is the use of unimolecular micelles.<br/><br/>Previous work in our lab has demonstrated the ability of heterografted amphiphilic double-brushes with poly(glycidyl methacrylate) (PGMA) backbone bearing poly(ethylene glycol) (PEG) and poly(D,L-lactide) (PLA) side chains to form extended cylindrical unimolecular micelles when transferred into a selective solvent. In the presence of a solute, such brushes underwent a conformational worm-to-sphere transition, as determined by TEM imaging and small-angle neutron scattering. Herein, we discuss that modifying the double-brush by grafting longer hydrophilic side chains restricts the solute-induced conformational changes observed earlier, leading to drug-loaded worm-like carriers.The effect of physicochemical properties of the solute on nanoparticle morphology is also discussed and contrasted to a linear diblock copolymer system to obtain greater insight on encapsulation behavior in brush copolymers. Regarding the solute, we observed that the brush aggregation can be precluded only if the hydrophobic interaction between the core-forming block and the solute is a favorable one, thus resulting in well-defined single molecule particles.

Unimolecular nanoparticles from highly branched amphiphilic macromolecules: Polymer self-assembly and solute stabilization

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.