Biodegradable calcium carbonate carriers for the topical delivery of clobetasol propionate

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 12; no. 2; pp. 4867 - 4881
• Main Authors: Saveleva, Mariia S, Verkhovskii, Roman A, Demina, Polina A, Surkov, Yury I, Anisimov, Roman A, Prikhozhdenko, Ekaterina S, Pidenko, Pavel S, Serebryakova, Isabella A, Zaytsev, Sergey M, Tuchin, Valery V, Svenskaya, Yulia I
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 22.05.2024
• Subjects: Administration, Topical; Animals; Anti-inflammatory agents; Bioavailability; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biodegradability; Biodegradation; Calcium carbonate; Calcium Carbonate - chemistry; Clobetasol - administration & dosage; Clobetasol - chemistry; Clobetasol - pharmacology; Dermatology; Drug Carriers - chemistry; Follicles; Glucocorticoids; Hair; Humans; Inflammation; Localization; Male; Particle Size; Propionic acid; Rats; Side effects; World population
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d4tb00303a

Inflammatory dermatoses represent a global problem with increasing prevalence and recurrence among the world population. Topical glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs in dermatology due to a wide range of their therapeutic actions, which, however, have numerous local and systemic side effects. Hence, there is a growing need to create new delivery systems for GCs, ensuring the drug localization in the pathological site, thus increasing the effectiveness of therapy and lowering the risk of side effects. Here, we propose a novel topical particulate formulation for the GC clobetasol propionate (CP), based on the use of porous calcium carbonate (CaCO 3 ) carriers in the vaterite crystalline form. The designed carriers contain a substantially higher CP amount than conventional dosage forms used in clinics (4.5% w/w vs. 0.05% w/w) and displayed a good biocompatibility and effective cellular uptake when studied in fibroblasts in vitro . Hair follicles represent an important reservoir for the GC accumulation in skin and house the targets for its action. In this study, we demonstrated successful delivery of the CP-loaded carriers (CP-CaCO 3 ) into the hair follicles of rats in vivo using optical coherent tomography (OCT). Importantly, the OCT monitoring revealed the gradual intrafollicular degradation of the carriers within 168 h with the most abundant follicle filling occurring within the first 48 h. Biodegradability makes the proposed system especially promising when searching for new CP formulations with improved safety and release profile. Our findings evidenced the great potential of the CaCO 3 carriers in improving the dermal bioavailability of this poorly water-soluble GC. Vaterite carriers were used to design a novel topical formulation for clobetasol propionate, which was capable of intrafollicular accumulation. Gradual degradation of the carriers in skin in vivo paves the way for improved safety and release profile.