Background: Dissolving microneedles (DMNs) have been used for skin restoration and wrinkle improvement. Although lipophilic compounds, for example, natural oils or ceramides, enrich the skin barrier, their delivery via DMNs is challenging because of DMN fabrication difficulties. Objectives: In the present study, we combined a topical formulation and a DMN patch to perform two-phase delivery comprising a lipophilic formulation and hydrophilic compound-loaded DMNs to improve skin barrier status and the efficacy of drug delivery. Methods: Horse oil-spread and adenosine-loaded DMN arrays were developed in a single patch (HOS-Ad-DMN patch). In vitro analysis was conducted to confirm the successful delivery of the compositions. Clinical assessments were conducted on the lateral canthus of 20 women to compare the efficacy of HOS-Ad-DMN patches with that of adenosine-loaded DMN patches (Ad-DMN patches). Results: Adenosine was delivered via the DMNs after skin penetration and horse oil was delivered successfully into the skin through the microchannels created by the Ad-DMNs. Compared with Ad-DMN patches, HOS-Ad-DMN patches significantly improved skin elasticity, hydration, dermal density, and wrinkles. No adverse events were observed. Conclusion: HOS-Ad-DMN patches are a safe and efficient system for skin restoration and wrinkle improvement.
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