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.

Toward smart self-accumulating bio-inspired drug carriers for improved topical efficacy in dermatology - Medicine Innovates
Figure 1: Conceptual schematic of this study: colloidal bio-inspired apatite nanoparticles (NP) may be used as drug carriers for topical delivery to the skin and hair follicles while limiting/avoiding side effects linked with skin penetration.

About the author

Prof. Christophe Drouet is a CNRS Senior Scientist, leader of the “Phosphates, Pharmacotechnics, Biomaterials” (PPB) research group of the CIRIMAT laboratory, University of Toulouse, France. Ph.D. in Materials Sciences. Major research fields include the physico-chemistry and thermochemistry of natural or synthetic (bio)minerals and the study of the surface characterization and reactivity of (bio)nanomaterials. Some key milestones include ~3 years spent as Research Associate at the University of California at Davis (UCDavis), USA, to study the thermochemistry/stability studies of various hydrated mineral phases; as well as other stays including at the University of Madrid, Spain, for specialization in the exploration of the surface of solids via X-ray photoelectron spectroscopy and via the follow-up of molecular adsorption processes.

A special focus in C. Drouet’s research is dedicated to the investigation of calcium phosphates and related compounds, in particular of biomimetic nanocrystalline apatites analogous to bone mineral, in view of innovative bio-medical applications as in bone repair and nanomedicine. He has especially contributed to the development of the “hydrated layer model” on the surface of apatite nanocrystals, as well as to a “cold sintering” approach by low-temperature-SPS to consolidate metastable calcium phosphates, and to the development of colloidal multifunctional apatite-based nanoparticles for use in nanomedicine: he has especially developed bio-inspired strategies for use in bone regeneration but also in oncology, hematology and dermatology.

C. Drouet received the honorary Racquel Legeros Award in June 2013 and the ISCM Excellence Award in 2016, for his contribution to the field of calcium phosphates research.


Choimet M, Tourrette A, Marsan O, Rassu G, Drouet C. Bio-inspired apatite particles limit skin penetration of drugs for dermatology applications. Acta Biomater. 2020 Jul 15;111:418-428.

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