Development of branched polyphenolic poly(beta amino esters) to facilitate post-synthesis processing

Given their versatility and formability, polymers have proven to be a viable platform facilitating a controlled and tuned release for a variety of therapeutic agents. One growing area of polymer drug delivery is polymeric prodrugs, which covalently link active pharmaceutical ingredients to a polymeric form to enhance stability, delivery, and pharmacology. One such class of polymeric prodrugs, poly(beta amino esters) (P beta AEs) can be synthesized into crosslinked, or thermoset, networks which greatly limits their processability. An antioxidant-P beta AE polymer prodrug that is soluble in organic solutions would permit enhanced processability, increasing their utility and manufacturability. Curcumin P beta AEs were synthesized to be soluble in organic solvents while retaining the release and activity properties. To demonstrate the polymer processability, curcumin P beta AEs were further synthesized into nanoparticles and thin films. Control over nanoparticle size and film thickness was established through variance of dope solution concentration and withdrawal speed, respectively. Layering of polymeric films was demonstrated through inkjet printing of thin films. Polymer function was characterized through curcumin release and antioxidant activity. The processing of the polymer had a drastic impact on the curcumin release profiles indicating the polymer degradation was influenced by surface area and porosity of the final product. Previously, release was controlled primarily through the hydrophobicity of the polymer. Here, we demonstrate a novel method for further tuning the degradation by processing the polymer.

Automated summary

Polymeric prodrugs, such as poly(beta amino esters) (P beta AEs), linking active pharmaceutical ingredients to a polymeric form, have shown great potential in controlled drug delivery. In this study, an antioxidant-P beta AE polymer prodrug that is soluble in organic solutions was synthesized to enhance the processability of the polymer. Curcumin P beta AEs were further processed into nanoparticles and thin films, with control over size and thickness. The processing of the polymer had a significant impact on the release profiles of curcumin, indicating the potential of tuning degradation through polymer processing.