Busatto C A, Labie H, Lapeyre V, Auzely-Velty R, Perro A, Casis N, Luna J, Estenoz D A, Ravaine V
Instituto de Desarrollo Tecnológico para la Industria Química, INTEC (Universidad Nacional del Litoral and CONICET), Güemes 3450, 3000 Santa Fe, Argentina.
Université de Bordeaux, Bordeaux INP, ISM, UMR 5255, Site ENSCBP, 16 avenue Pey Berland, 33607 Pessac, France.
J Colloid Interface Sci. 2017 May 1;493:356-364. doi: 10.1016/j.jcis.2017.01.029. Epub 2017 Jan 10.
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.
聚合物微凝胶因其在生物医学领域作为药物递送系统的巨大潜力而受到广泛关注。透明质酸（HA）是一种天然存在的糖胺聚糖，由N-乙酰-D-葡萄糖胺和D-葡萄糖醛酸组成。这种聚合物具有生物可降解性、无毒且可进行化学修饰。在本研究中，提出了一种用于制备包裹疏水性药物的可生物降解HA微凝胶的共流微流控策略。该方法基于：（i）通过超声法制备初级水包油（O/W）纳米乳液；（ii）利用微流控技术形成双油包水包油乳液（O/W/O）；（iii）通过存在于液滴水相中的甲基丙烯酸酯基团修饰的HA前体（HA-MA）的光聚合作用使微凝胶交联。该过程用于孕酮的包封和控释。在37°C下，于存在不同浓度透明质酸酶的PBS缓冲液中进行了降解性以及包封/释放研究。结果表明，酶促降解可用于触发微凝胶中孕酮的释放。该方法可对释放系统进行精确控制，并可应用于不同类型疏水性药物的包封和控释。
