Nanocarrier System Based on Jabuticaba Peel Co-Products and Caffeine for Photoprotective and Regenerative Skin Applications

Background: Ultraviolet (UV) radiation, urban pollution and depletion of cutaneous antioxidant reserves are interconnected drivers of photoaging, matrix metalloproteinase (MMP) activation, mitochondrial dysfunction and dermal extracellular matrix degradation. Plant polyphenols can counteract these processes, but topical efficacy is limited by chemical instability, polarity-driven partitioning and a hostile stratum corneum delivery interface. Here we report a green nanostructured lipid carrier co-loading a phenolic-rich jabuticaba (Plinia cauliflora) peel extract and caffeine (NLC-JC), engineered with Amazonian lipids (Astrocaryum murumuru butter and Orbignya phalerata oil) and stabilized by a Natural Deep Eutectic Solvent (NaDES)-like microenvironment. Methods: UPLC profiling was used to determine the polyphenolic composition of the extract. Physicochemical characterization included hydrodynamic diameter and PDI, ζ-potential, lipid matrix organization (XRD) and morphology (TEM), as well as colloidal stability over 30 days. Cytotoxicity was assessed in SH-4 melanocytes (ISO 10993-5) and in zebrafish (Danio rerio) embryos (96-h IC50, GHS acute hazard threshold). Functional antioxidant and photoprotective activity was evaluated by DPPH radical scavenging, and by attenuation of UVC- and H2O2-induced anion superoxide generation, alongside assessment of cellular and nuclear morphology under combined oxidative stress. Results: UPLC profiling revealed a polyphenolic fingerprint dominated by ellagic acid (476.8 ± 19.7 µg g−1), quercetin-3-rhamnoside (90.9 ± 4.6 µg g−1), quercetin (83.7 ± 1.4 µg g−1), cyanidin-3-glucoside (73.0 ± 1.2 µg g−1) and protocatechuic acid (68.2 ± 2.2 µg g−1), bioactives with documented anti-MMP, NF-κB-suppressing and ROS-scavenging activities. Optimized NLC-JC showed a hydrodynamic diameter of 56.1 nm (PDI = 0.131), negative ζ-potential, amorphous lipid matrix (XRD) and spherical morphology (TEM, ≈150–200 nm electron-dense particles), with 30-day colloidal stability. NLC-JC exhibited low cytotoxicity in SH-4 melanocytes (IC50 = 2304 μg mL−1), preserving ≥70% viability across the cosmetically relevant range (ISO 10993-5), and a 96-h LC50 of 2013 μg mL−1 in zebrafish (Danio rerio) embryos, three orders of magnitude above the GHS acute hazard threshold (100 mg L−1). Functionally, NLC-JC produced ≈50% DPPH radical scavenging at concentrations comparable to ascorbic acid, attenuated UVC- and H2O2-induced anion superoxide generation and preserved cellular and nuclear morphology under combined oxidative stress. Conclusion: These data position NLC-JC as a safe-by-design, multifunctional dermocosmetic platform combining agro-industrial valorization with mechanism-anchored photoprotection.