C.A. Busatto, H. Labie, V. Lapeyre, R. Auzely-Velty, A. Perro, N. Casis, J. Luna, D.A. Estenoz, V. Ravaine

Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets. The procedure is used for the encapsulation and controlled release of progesterone. Degradability and encapsulation/release studies in PBS buffer at 37 °C in presence of different concentrations of hyaluronidase are performed. It is demonstrated that enzymatic degradation can be used to trigger the release of progesterone from microgels. This method provides precise control of the release system and can be applied for the encapsulation and controlled release of different types of hydrophobic drugs.