Thermosensitive Alginate/Carrageenan-Stearic Acid Dissolving Microneedles Incorporating Liposome-Coated Hollow Mesoporous Silica Nanoparticles for Controlled Caffeine Delivery.

Caffeine is a promising active for topical pharmaceutical and cosmetic applications; however, its hydrophilic nature can limit passive transport across the stratum corneum and reduce local retention. Although nanoparticle-loaded dissolving microneedles have been explored, few systems combine a hollow porous carrier, a lipid coating, and a polysaccharide matrix within a single controlled-release platform. This study developed thermosensitive dissolving microneedles (DMNs) incorporating caffeine-loaded liposome-coated hollow mesoporous silica nanoparticles (ULp-Caf@HMSNs). Sodium alginate-κ-carrageenan matrices, with and without stearic acid modification, were evaluated for their effects on thermal behavior, mechanical strength, and caffeine release. HMSNs showed a hollow mesoporous structure and high specific surface area, while FTIR supported successful incorporation of the formulation components. Liposome coating increased particle size while maintaining nanoscale dimensions. Hot-stage microscopy showed temperature-dependent structural changes at approximately 33-35 °C, with lower apparent transition temperatures in stearic acid-containing formulations. All DMNs exhibited compression forces comparable to mechanically competent DMNs, with NaAlg-κ-car systems reaching 14.3-15.1 N per array. Free-caffeine DMNs followed non-Fickian release, whereas ULp-Caf@HMSN-containing formulations followed Higuchi diffusion-controlled release and showed slower caffeine release. Stearic acid did not consistently improve release performance. The novelty of this work lies in integrating a hollow silica reservoir, a liposomal coating, and an alginate-κ-carrageenan microneedle matrix within one platform. Overall, the system provides a basis for further evaluation in controlled topical or transdermal caffeine delivery.