Postpolymerization Modification of Poly(2-vinyl-4,4-dimethyl azlactone) as a Versatile Strategy for Drug Conjugation and Stimuli-Responsive Release
Document Type
Article
Publication Date
3-8-2024
Department
Biological Sciences
School
Biological, Environmental, and Earth Sciences
Abstract
Postpolymerization modification of highly defined “scaffold” polymers is a promising approach for overcoming the existing limitations of controlled radical polymerization such as batch-to-batch inconsistencies, accessibility to different monomers, and compatibility with harsh synthesis conditions. Using multiple physicochemical characterization techniques, we demonstrate that poly(2-vinyl-4,4-dimethyl azlactone) (PVDMA) scaffolds can be efficiently modified with a coumarin derivative, doxorubicin, and camptothecin small molecule drugs. Subsequently, we show that coumarin-modified PVDMA has a high cellular biocompatibility and that coumarin derivatives are liberated from the polymer in the intracellular environment for cytosolic accumulation. In addition, we report the pharmacokinetics, biodistribution, and antitumor efficacy of a PVDMA-based polymer for the first time, demonstrating unique accumulation patterns based on the administration route (i.e., intravenous vs oral), efficient tumor uptake, and tumor growth inhibition in 4T1 orthotopic triple negative breast cancer (TNBC) xenografts. This work establishes the utility of PVDMA as a versatile chemical platform for producing polymer-drug conjugates with a tunable, stimuli-responsive delivery.
Publication Title
Biomacromolecules
Recommended Citation
Mohammad, S.,
Toragall, V. B.,
Fortenberry, A.,
Shofolawe-Bakare, O.,
Sulochana, S.,
Heath, K.,
Owolabi, I.,
Tassin, G.,
Flynt, A. S.,
Smith, A. E.
(2024). Postpolymerization Modification of Poly(2-vinyl-4,4-dimethyl azlactone) as a Versatile Strategy for Drug Conjugation and Stimuli-Responsive Release. Biomacromolecules.
Available at: https://aquila.usm.edu/fac_pubs/21641