Galindo Ruth, Sánchez-López Elena, Gómara María José, Espina Marta, Ettcheto Miren, Cano Amanda, Haro Isabel, Camins Antoni, García María Luisa
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, 08034 Barcelona, Spain.
Pharmaceutics. 2022 Jan 26;14(2):285. doi: 10.3390/pharmaceutics14020285.
Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed. Additionally, to avoid fast clearance and increase cellular internalization into the ocular tissues, PLGA nanoparticles have been functionalized using PEG and cell penetrating peptides (Tet-1 and B6). To optimize the formulations, a factorial design was carried out and short-term stability of the nanoparticles was studied. Moreover, morphology was also observed by transmission electron microcopy and in vitro drug release was carried out. Ocular tolerance of the formulations was ensured in vitro and in vivo and anti-inflammatory therapeutic efficacy was also assessed. Surface functionalized nanoparticles loading Licochalcone-A were developed with an average size below 200 nm, a positive surface charge, and a monodisperse population. The formulations were non-irritant and showed a prolonged Licochalcone-A release. Despite the fact that both Licochalcone-A Tet-1 and B6 functionalized nanoparticles demonstrated to be suitable for the treatment of ocular inflammation, B6 targeted nanoparticles provided greater therapeutic efficacy in in vivo assays.
甘草查尔酮A是一种具有抗炎特性的天然化合物。然而，它的水溶性较低，这使得其在眼部炎症治疗中的应用变得困难。为了克服这一缺点，已开发出包含甘草查尔酮A的可生物降解纳米颗粒。此外，为了避免快速清除并增加细胞向眼部组织的内化，聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒已用聚乙二醇（PEG）和细胞穿透肽（Tet-1和B6）进行了功能化修饰。为了优化制剂，进行了析因设计并研究了纳米颗粒的短期稳定性。此外，通过透射电子显微镜观察了形态，并进行了体外药物释放实验。在体外和体内确保了制剂的眼部耐受性，并评估了抗炎治疗效果。已开发出负载甘草查尔酮A的表面功能化纳米颗粒，其平均尺寸低于200纳米，表面带正电荷，且粒径分布均匀。这些制剂无刺激性，并显示出甘草查尔酮A的缓释特性。尽管甘草查尔酮A Tet-1和B6功能化纳米颗粒均被证明适用于眼部炎症的治疗，但在体内实验中，B6靶向纳米颗粒具有更高的治疗效果。
