Varrica Carla, Carvalheiro Manuela, Faria-Silva Catarina, Eleutério Carla, Sandri Giuseppina, Simões Sandra
Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.
Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
Bioengineering (Basel). 2021 Nov 28;8(12):192. doi: 10.3390/bioengineering8120192.
Nanostructured lipid carriers (NLC) have been widely studied as delivery systems for a variety of routes, including the skin. Their composition results in an imperfect lipid matrix, allowing increased drug encapsulation. Allopurinol (AP), a xanthine oxidase inhibitor, is characterized by low water solubility and high melting point, which has hampered its use through the topical route. In this work, AP was incorporated in a NLC formulation to enhance drug-carrier association and skin delivery as a topical approach to treat wounds. AP-NLC system was characterized in terms of size, charge, rheological behavior, and in vitro skin permeation. The in vitro cytotoxicity was evaluated using HaCaT cells. The wound healing efficacy of the AP-NLC formulation on animal skin lesions was evaluated in male Wistar rats. The AP-NLC presented a mean size of 193 ± 15 nm with a PdI of 0.240 ± 0.02, zeta potential values around -49.6 mV, and an encapsulation efficiency of 52.2%. The AP-NLC formulation presented an adequate profile to be used topically, since epidermal and dermal drug retention were achieved. No reduction in HaCaT cells viability was observed at the tested concentrations (AP < 10 μg/mL). The in vivo application of the AP-NLC formulation resulted in the regeneration of skin lesions when compared with non-treated controls.
纳米结构脂质载体（NLC）作为包括皮肤在内的多种给药途径的递送系统已得到广泛研究。它们的组成导致脂质基质不完善，从而增加药物包封率。别嘌醇（AP）是一种黄嘌呤氧化酶抑制剂，其特点是水溶性低、熔点高，这限制了其通过局部给药途径的应用。在本研究中，将AP掺入NLC制剂中，以增强药物与载体的结合以及皮肤递送，作为治疗伤口的局部给药方法。对AP-NLC系统进行了粒径、电荷、流变学行为和体外皮肤渗透等方面的表征。使用HaCaT细胞评估体外细胞毒性。在雄性Wistar大鼠中评估了AP-NLC制剂对动物皮肤损伤的伤口愈合效果。AP-NLC的平均粒径为193±15nm，多分散指数（PdI）为0.240±0.02，zeta电位值约为-49.6mV，包封率为52.2%。AP-NLC制剂呈现出适合局部应用的特性，因为实现了表皮和真皮中的药物滞留。在测试浓度下（AP<10μg/mL）未观察到HaCaT细胞活力降低。与未处理的对照组相比，AP-NLC制剂的体内应用导致皮肤损伤再生。
