Bottlebrush Polymer Excipients Enhance Drug Solubility: Influence of End-Group Hydrophilicity and Thermoresponsiveness

Monica L. Ohnsorg, Paige C. Prendergast, Lindsay L. Robinson, Matthew R. Bockman, Frank S Bates, Theresa M. Reineke

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Bottlebrush polymers have great potential as vehicles to noncovalently sequester, stabilize, and deliver hydrophobic small molecule actives. To this end, we synthesized a poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) bottlebrush copolymer using ring-opening metathesis polymerization and developed a facile method to control the thermoresponsive properties using postpolymerization modification. Six increasingly hydrophilic end-groups were installed, yielding cloud point temperature control over a range of 22-42 °C. Solubility enhancement of the antiseizure medication, phenytoin, increased significantly with the hydrophilicity of the end-group moiety. Notably, carboxylated bottlebrush copolymers solubilized formulations with higher drug loadings than linear copolymers because they exist as unimolecular nanoparticles with a synthetically defined density of polymer chains that are more stable in solution. This work provides the first investigation of bottlebrush polymers for hydrophobic noncovalent sequestration and solubilization of pharmaceuticals.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalACS Macro Letters
Issue number3
StatePublished - Feb 16 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.

How much support was provided by MRSEC?

  • Partial

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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