Silk Sericin Functionalized with Carboxy Drugs for Dermocosmetic Applications.

Silk sericin protein, a textile industry by-product showing no toxicity on oral/topical administration, has recently been exploited as a drug delivery system. The high serine content in sericin makes its functionalization through covalent ester-type bonds feasible; however, only in a few cases have covalent conjugates of sericin with the drug to be delivered been developed. In this paper, we report the preparation of sericin conjugates with carboxy drugs of dermatological interest, i.e., naproxen, retinoic acid, and azelaic acid. Characterization of the purified products by spectroscopic methods, particularly ATR-FTIR, provided evidence for the formation of the ester bond, while SDS-PAGE indicated a substantial modification of the protein. Proteomic analysis allowed the identification of drug-peptide adducts in the samples. The extent of ester functionalization (1-3 w/w%) was estimated by alkaline hydrolysis. No cytotoxicity of NAP@SER on HaCaT was observed over a broad range of concentrations. Ex vivo tests on defatted pig skin demonstrated effective passage of the free drug through the skin (5% w/w of the applied dose) from a NAP@SER glycerol suspension and a significant retention of the drug (33% w/w) within the dermal or epidermal tissues. These results hint at the potential of sericin conjugates as prodrugs for dermal administration.