Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA’s inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods. In vitro hydrolytic degradation analyses revealed KA release was drastically influenced by polymer backbone composition (e.g., poly(carbonate-ester) vs polyester), linker molecule (aliphatic vs heteroatom-containing), and release conditions (physiological vs skin). Tyrosinase inhibition assays demonstrated that aliphatic KA dienols, the major degradation product under skin conditions, were more potent then KA itself. All dienols were found to be less toxic than KA at all tested concentrations. Additionally, the most lipophilic dienols were statistically more effective than KA at inhibiting melanin biosynthesis in cells. These KA-based polymer systems deliver KA analogues with improved efficacy and cytocompatible profiles, making them ideal candidates for sustained topical treatments in both medical and personal care products.
The bioaccessibility of salicylic acid (SA) can be effectively modified by incorporating the pharmacological compound directly into polymers such as poly(anhydride-esters). After simulated digestion conditions, the bioaccessibility of SA was observed to be statistically different (p < 0.0001) in each sample: 55.5 ± 2.0% for free SA, 31.2 ± 2.4% the SA-diglycolic acid polymer precursor (SADG), and 21.2 ± 3.1% for SADG-P (polymer). The release rates followed a zero-order release rate that was dependent on several factors, including (1) solubilization rate, (2) macroscopic erosion of the powdered polymer, (3) hydrolytic cleavage of the anhydride bonds, and (4) subsequent hydrolysis of the polymer precursor (SADG) to SA and diglycolic acid.
To reduce raw material consumption and increase synthetic efficiency, bioactive‐based poly(anhydride‐esters) containing aliphatic dicarboxylic acid‐linkages and bioactives, salicylic and p‐hydroxybenzyl acid, are synthesized via one‐pot melt‐condensation polymerizations. One‐pot poly(anhydride‐esters) physicochemical characteristics, molecular weight, and thermal properties are analyzed and compared. One‐pot salicylic acid‐based poly(anhydride‐esters) are further evaluated against analogous polymers synthesized via established methods, possessing statistically similar polymer and thermal properties while drastically reducing reaction time and solvent usage. Interestingly, p‐hydroxybenzyl acid‐based poly(anhydride‐ester) synthesis is temperature‐dependent, as higher reaction temperatures facilitate polyester formation. Compared to their poly(anhydride‐ester) analogs, these are found to possess improved thermal properties and higher molecular weight while. Accelerated hydrolytic degradation studies confirm complete bioactive release and polymer degradation. Furthermore, polymer cytotoxicity studies using 3T3 mouse fibroblasts show all polymers to be cytocompatible above therapeutically relevant concentrations. This method demonstrates that the synthesis of high‐yielding monomers can be followed by melt‐condensation polymerization in situ for the synthesis of polyanhydrides and their derivatives.
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