Toward smart self-accumulating bio-inspired drug carriers for improved topical efficacy in dermatology

The skin serves as a natural barrier for the body, however several skin disorders may compromise the skin integrity if not correctly treated, such as eczema, acne and contact dermatitis. Orally administered drugs can be used to treat such skin disorders but they access the blood stream and may cause various side effects. This has made the topical application of drugs relevant in dermatology so as to limit side effects and ensure direct delivery of the active components to the skin. Nevertheless, even with topical application, partial drug permeation may still occur thus also possibly generating undesirable side effects. It is therefore essential that strategies to restrict the action of the drug to the surface of the skin be developed. There have been studies on direct drug delivery, for example at the hair follicles, with the use of drug nanocarriers, however no ideal system has been found to date as systems had limited chemical stability, efficacy or biocompatibility.

In this study, French scientists from the CIRIMAT Institute (University of Toulouse): Prof. Christophe Drouet (leader), Dr. Audrey Tourrette, Maëla Choimet, and Olivier Marsan collaborated with Dr. Giovanna Rassu from the University of Sassari in Italy. They explored the use of colloidal submicron mineral/organic hybrid particles based on bio-inspired calcium phosphate apatite, for the first time as drug carriers for topical applications. Results showed that the association of the drug onto such apatite particles favors skin surface effects thanks to the accumulation of the particles at the skin surface and at hair follicles, thus restraining drug penetration across the skin and opening new opportunities for smart drug delivery to the skin with limited side effects. The research work was recently published in the journal Acta Biomaterialia, a leading journal in biomaterials and (nano)medicine.

The research team first prepared and characterized the colloidal particles based on bio-inspired calcium phosphate apatite stabilized by size-monitored phosphonated polyethyleneglycol (PEGp). The mineral core of the particles was composed of nanocrystalline apatite which is very similar to bone mineral, thus exhibiting a high intrinsic biocompatibility. They then conducted permeation tests in both static and dynamic conditions using artificial and biological (porcine epidermis) membranes to mimic skin layers. They observed that the association of a model drug (Folic acid) to apatite colloidal particles resulted in a sharp decrease in the drug permeation across both synthetic and biological membranes compared to when a Folic acid solution with “free” solubilized molecules was used, imitating a regular drug formulation.

Furthermore, with the use of europium-labeled apatite nanoparticles, the research team investigated the particles’ localization following drug application on porcine ear skin explants. They developed a strategy coupling histology, Raman confocal microscopy and photoluminescence in order to trace the particles’ localization. The incorporation of luminescent europium ions into the particles allowed localizing them precisely: they appeared gathered onto the outer layer of the skin and at the entrance of hair follicles, that is where the action of most dermatological treatment is needed. In contrast, when the europium ions were in a dissolved state in aqueous solution – mimicking again solubilized species in a regular formulation – the ions were disseminated well beyond the skin surface (infundibulum, epidermis invagination and in the dermal zone).

Overall, the study successfully demonstrated that bio-inspired colloidal apatite submicron particles can be used as new smart drug carriers for significantly favoring topical delivery. The association of drug molecules to such apatite particles may indeed significantly favor skin surface effects while limiting/avoiding side effects linked to drug permeation across the skin. These findings are novel and will serve as a foundation for the future application of bio-inspired calcium phosphate apatite in the field of dermatology.