Dextrin Palmitate and Disteardimonium Hectorite Construct a Gel-like EHMC Matrix: Enhanced UVB Photoprotection and Plasma Exposure Modulation

2-Ethylhexyl-4-methoxycinnamate (EHMC) is among the most widely adopted organic UVB filters in commercial sunscreens. Nevertheless, its practical application potential is limited by unfavorable formulation compatibility and safety risks stemming from systemic exposure after topical administration. In this study, an oil-continuous structured gel matrix consisting of EHMC, disteardimonium hectorite (DDH) and dextrin palmitate (DP) was constructed to enhance UVB photoprotection and modulate the plasma exposure profile of EHMC following topical application. Comprehensive characterizations including rheology, XRD, Raman spectroscopy, FTIR spectroscopy, TGA and SEM collectively revealed that the combined incorporation of DDH and DP facilitates matrix structural rearrangement, enables EHMC to bind within the structured network, and promotes the formation of more intact continuous surface films. In vitro SPF assays demonstrated that the finished topical formulation SC-4 delivered superior UVB blocking efficacy compared with the EHMC-only control SC-1; furthermore, SC-4 exhibited improved short-term physical stability under the preset thermal and centrifugal acceleration test conditions. Follow-up skin safety assessments, mass spectrometry imaging (MSI) and pharmacokinetic assays verified that SC-4 elicited no remarkable acute skin irritation across all experimental conditions. Relative to SC-1, the reference formulation with EHMC as the sole UV filter, SC-4 displayed weaker EHMC-related distribution signals in skin tissues, accompanied by lower early plasma EHMC concentrations and a slightly lower AUC0–48h trend. Collectively, these findings indicate that DDH/DP co-assembly serves as a viable matrix-structuring strategy to modulate EHMC-related skin distribution and early plasma exposure. Further research into UVA blocking performance, photostability, skin retention and transdermal permeation profiles, as well as long-term storage stability, is required to advance the development of broad-spectrum sunscreen formulations built on this novel matrix platform.