TY - JOUR
T1 - Bottlebrush Polymer Excipients Enhance Drug Solubility
T2 - Influence of End-Group Hydrophilicity and Thermoresponsiveness
AU - Ohnsorg, Monica L.
AU - Prendergast, Paige C.
AU - Robinson, Lindsay L.
AU - Bockman, Matthew R.
AU - Bates, Frank S.
AU - Reineke, Theresa M.
N1 - Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.
PY - 2021/3/16
Y1 - 2021/3/16
N2 - 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.
AB - 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.
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U2 - 10.1021/acsmacrolett.0c00890
DO - 10.1021/acsmacrolett.0c00890
M3 - Article
C2 - 35549060
AN - SCOPUS:85101972134
SN - 2161-1653
VL - 10
SP - 375
EP - 381
JO - ACS Macro Letters
JF - ACS Macro Letters
IS - 3
ER -