Core–Shell Bottlebrush Polymers: Unmatched Delivery of Small Active Compounds Deep Into Tissues

Abstract

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers—characterized by variations in backbone length, grafting density, and self-assembly morphology—offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a “grafting-from” strategy. Comprehensive characterization techniques, including nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and atomic force microscopy (AFM), employed to confirm the polymers’ structure. The BB polymers evaluated as carriers for molecules with differing hydrophobicity profiles, namely Rhodamine B and Paclitaxel. These nanocarriers systematically assessed for drug loading efficiency and penetration capabilities, compared to conventional polymeric micelles (PM) formed from linear amphiphilic polymers. BB-based nanocarriers exhibited superior cellular uptake in both 2D and 3D cell culture models when compared to PM. Furthermore, analysis of drug distribution and particle penetration highlighted the profound influence of polymer morphology on biological interactions. These findings underscore the potential of unimolecular carriers with precisely defined structures as promising drug delivery platforms for a wide range of biomedical applications.