Biodegradable emulsions for the co-encapsulation and the release of active pharmaceutical ingredients – ELiSA

Pickering emulsions are non-miscible liquid dispersions stabilized with particles instead of surfactants. In this project, emulsions stabilized with biodegradable and biocompatible nanoparticles (NP) for pharmaceutical use will be formulated. Biodegradable and biocompatible Pickering emulsions have the advantage of being potentially less toxic or irritant compared to emulsions stabilized with synthetic surfactants or mineral particles. Furthermore, it would also be possible to incorporate two active pharmaceutical ingredients (API) in the same formulation: the first associated with NP, and the second dissolved in the droplets of the emulsion. This will result in a very innovative drug delivery system: a biodegradable and biocompatible emulsion carrying two different API in the same dosage form.
Our main objective is to formulate long-term stabilized oil in water emulsions, using Miglyol (oil composed of medium-chain triglycerides and widely used in pharmacy) and biodegradable and biocompatible PLGA (poly (lactic-co-glycolic) acid) NP in order to stabilize the emulsion. This system will be used to co-encapsulate two active pharmaceutical ingredients (API): one in the NP and the other in the emulsion droplets. The simultaneous delivery of two different API from a single biodegradable and biocompatible dosage form, which can potentially act at different levels locally and with different kinetics, will constitute a major and innovative achievement in drug delivery. This will enhance the efficiency of the dosage form and improve the patient’s adherence to the treatment.
Modern concepts of physico-chemistry and pharmaceutical technology will be used to challenge current topical treatments for psoriasis, a common skin disease with strong social and health impact. A combination therapy using two API used to treat psoriasis, i.e. cyclosporine (loaded in the PLGA NP) and calcitriol (dissolved in the oil droplets) could allow to obtain maximum improvements with minimum side effects. Strong benefits are also expected in dosage form with a single API: the fact that the same API can be encapsulated in the droplets and/or in the NP will allow a better controlled drug release, as it will offer simultaneously two levels of drug release (one from the NP, one from the droplets), with potentially different kinetics.
In this project, a thorough physical chemistry study will be performed, to the benefit of pharmaceutical applications. Different PLGA NP will be prepared and used to formulate and optimize biodegradable Pickering water/Miglyol emulsions (first, without API), and a thorough study will be performed to clarify the stabilization mechanism of the water/oil interface in presence of NP. Thereafter, emulsions containing the API will be prepared, and in vitro transdermal delivery experiments will allow to study the kinetics of diffusion of the API through a model membrane and through human skin explants. Localization of the NP in human skin explants will also be determined, and the biological consequences on epidermal cells, including keratinocytes and Langerhans cells, will be analyzed after topical application of the emulsions. Finally, the efficiency of our emulsions will be tested during pre-clinical experiments.