Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752/405, Porto Alegre, RS, CEP 90610-000, Brazil.
AAPS PharmSciTech. 2020 Jan 6;21(2):54. doi: 10.1208/s12249-019-1558-x.
Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 μmol L) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.
宫颈癌与人类乳头瘤病毒(HPV)有关,现已成为女性中第四大常见癌症。该疾病的治疗方法之一是基于咪喹莫特的应用。在这项研究中,我们假设纳米乳剂中的咪喹莫特的使用比非封装形式的药物在治疗宫颈癌方面具有更好的抗肿瘤效果。使用阴道黏膜作为膜进行了渗透性研究,以及涉及宫颈癌细胞的体外研究(活力、集落形成试验和细胞死亡分析)。我们表明,少量封装的咪喹莫特渗透了阴道黏膜。然而,与游离药物相比,用低浓度(3.0 μmol/L)的制剂处理后,更多的细胞死亡。此外,该创新制剂表现出涉及自噬和细胞凋亡的细胞死亡组合机制。我们的研究结果表明,负载咪喹莫特的纳米乳剂可以作为治疗宫颈癌的替代产品,验证了这一假设。