Nanostructured Lipid Carriers Enhance In Vitro Skin Delivery of Enzymatically Extracted Bombyx mori Silk Cocoon Bioactives: Development and Clinical Evaluation of an Anti-Aging Facial Serum

Background/Objectives: This study investigated the potential of nanostructured lipid carriers (NLCs) to improve the in vitro skin delivery and retention of bioactive compounds derived from Bombyx mori silk cocoon. Furthermore, an NLC-based facial serum was developed and clinically evaluated for its efficacy and safety. Methods: Silk cocoons from Nang Lai (NL) and Lueang Saraburi (LS) were extracted using aqueous and enzymatic methods. Extracts were evaluated for protein, phenolic, and flavonoid contents, antioxidant activity, collagenase inhibition, and irritation potential. The most active extract was incorporated into NLCs and assessed for their physicochemical properties, entrapment efficiency, release, and Strat-M® membrane permeation and retention. The selected NLC was subsequently incorporated into a facial serum and clinically evaluated in 30 volunteers over 28 days for its effects on skin hydration and roughness using a Corneometer® and Visioscan®, respectively. Results: Enzymatic extraction markedly increased phenolic and flavonoid contents, resulting in stronger antioxidant and collagenase inhibitory activities than aqueous extraction. LS enzymatic extract (LS-EN) exhibited the most favorable overall bioactivities and was selected for NLC formulation, which showed a particle size of 149 ± 1 nm, low polydispersity index (0.263 ± 0.05), a zeta potential of −48 ± 1 mV, and an entrapment efficiency of 83%. Compared with the solution, the NLCs showed sustained release and approximately 3.7-fold higher membrane retention (5.45 ± 0.59% versus 1.47 ± 0.59%). The NLC-based facial serum demonstrated good skin tolerability and high user satisfaction, with skin moisture increasing by 7.05% and skin roughness significantly decreasing by 6.74–7.29% after 28 days of application (p < 0.05). Conclusions: Enzymatic extraction combined with NLC encapsulation enhanced the cosmeceutical potential of silk cocoon bioactive by enabling sustained release and localized retention, while the NLC-based facial serum demonstrated good skin tolerability and improved skin hydration and roughness, supporting its potential as a promising anti-aging cosmeceuticals.