A Simple Non-Invasive Approach toward Efficient Transdermal Drug Delivery Based on Biodegradable Particulate System

Transdermal administration via skin appendages enables both localized and systemic drug delivery, as well as minimizes incidental toxicity. However, the design of an appropriate effective method for clinical use remains challenging. Here, we introduce calcium carbonate-based carriers for the transdermal transportation of bioactive substances. The proposed system presents easily manufacturable biodegradable particles with a large surface area enabling a high payload ability. Topical application of submicron porous CaCO3 particles in rats followed by the therapeutic ultrasound treatment results in their deep penetration through the skin along with plentiful filling of the hair follicles. Exploiting the loading capacity of the porous particles, we demonstrate efficient transportation of a fluorescent marker along the entire depth of the hair follicle down the bulb region. In vivo monitoring of the carrier degradation reveals the active dissolution/recrystallization of CaCO3 particles, resulting in their total resorption within 12 days. The proposed particulate system serves as an intrafollicular depot for drug storage and prolonged in situ release over this period. The urinary excretion profile proves the systemic absorption of the fluorescent marker. Hence, the elaborated transdermal delivery system looks promising for medical applications. The drug delivery to different target regions of the hair follicle may contribute to regenerative medicine, immunomodulation, and treatment of various skin disorders. In the meantime, the systemic uptake of the transported drug opens an avenue for prospective delivery routes beyond the scope of dermatology.