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    Biomaterials

    (A-18) Enhancing Drug Conjugation and Responsive Release through Post-Polymerization Modification of Poly(2-Vinyl-4,4-Dimethyl Azlactone)

    Friday, October 13, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row A - Poster # 18

      Presenting Author(s)

    • SK ARIF MOHAMMAD, PhD

      Postdoctoral Research Associate
      The University of Mississippi
      Oxford, Mississippi, United States

      • Co-Author(s)

    • FA

      Fortenberry Alex

      Graduate Student
      University of Mississippi, United States

    • AS

      Adam E. Smith

      Associate Professor
      University of Mississippi, United States

      • Primary Investigator(s)

    • Thomas A. Werfel

      Assistant Professor
      University of Mississippi, United States

    Introduction:: Post-polymerization 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 types of monomers, and compatibility with harsh synthesis conditions. Poly(2-vinyl-4,4-dimethyl azlactone) is an efficient reactive tool for post-polymerization modification with various small molecule drugs and biologics. We demonstrate the versatile nature of PVDMA scaffolds by modifying them with a coumarin-derivative (DBAC), doxorubicin, camptothecin, and 2-Dimethylaminoethanol (DMAE). In addition, we depicted controlled DBAC drug release from the PVDMA backbone. Moreover, we have shown the modification of PVDMA scaffolds with tertiary amine-containing alcohols for making charge-reversing nucleic acid delivery platforms and demonstrate the controlled DNA release from polyplexes.

    Materials and Methods:: For synthesized PVDMA scaffolds, we polymerized VDMA monomer via reversible addition−fragmentation chain-transfer (RAFT) polymerization technique. Next, we introduced ester moieties on the side chain of the PVDMA scaffold by post polymerization modification of PVDMA with DMAE and DBAC respectively. We studied the kinetics of drug release via dialysis process and monitored by UV-Vis spectroscopy. Further, we depicted charge-reversing nucleic acid delivery via the gel electrophoresis technique.

    Results, Conclusions, and Discussions:: Results and Discussion: We checked the 1H NMR, FTIR spectroscopy for structural characterization of PVDMA, and modified PVDMA polymers, spectroscopy data justified successfully formation of all the materials. We did kinetics of drug release studies at pH 5.5 and 7.4 buffer solutions at 37 ℃ and measured absorbance of coumarin at 316 nm by UV-Vis spectroscopy. Next, we investigated the ability of DMAE-modified PVDMA to release nucleic acid under physiologic conditions.

    Conclusion: PVDMA is a productive reactive method for post-polymerization modification using different small-molecule drugs and biologics. We use a coumarin derivative (DBAC), doxorubicin, camptothecin, and DMAE to modify PVDMA scaffolds in order to show their adaptability. We illustrated controlled DBAC drug release from the PVDMA support structure. Additionally, we have demonstrated the controlled DNA release from polyplexes.


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