Upcycling agri-food and industrial byproducts into high-value bio-nanomaterials represents a promising route for sustainable drug delivery. In this work, we describe the development and the physico-chemical characterization of a topical nanoformulation made up of sericin (4 mg/mL), a silk degumming byproduct, and elastin (2 mg/mL), a biopolymer derived from human connective tissue, enriched with resveratrol (RSV), a winemaking-derived polyphenol.
The nanoblends showed an average diameter of 140 nm, a narrow size distribution, a Zeta potential of -35 mV and high stability at pH 7 and 10 and temperatures between 32 °C and 37 °C. Lyophilization with 10% mannitol preserved particle size and polydispersity index, while the Zeta potential shifted to -24 mV. Encapsulation of RSV (0.4 mg/mL) achieved an entrapment efficiency of ~30% (drug content 0.12 mg/mL) without altering nanoparticle size. The release studies showed biphasic kinetics reaching a maximum cumulative leakage of 90% after 24 h. The Higuchi model provided the best fit (
), establishing Fickian diffusion as the primary release mechanism.
DPPH assay showed a superior radical scavenging activity for RSV-loaded nanoparticles compared to the free RSV (~63% vs ~36% at 10 µg/mL). In vitro tests on HaCaT cells confirmed the high biocompatibility of the formulation. RSV-loaded nanoblends demonstrated superior cytoprotection compared to the free drug (80–90% vs. 78–85% of cell viability at a drug concentration of 0.5-5 µM, respectively) when H2O2 was employed as an oxidant (700 µM). CellROX and MitoSOX assays confirmed the ability of RSV-loaded nanoblends to effectively reduce both intracellular and mitochondrial ROS production.
Finally, CompuSyn modeling validated strong carrier-drug synergy (CI < 1), showing maximum efficiency at a drug concentration of 10 µg/mL with a Dose Reduction Index of 3.00. These results demonstrate the antioxidant potential of sericin-elastin nanoblends containing RSV as an innovative cosmeceutical system.