Pensel Patricia E, Ullio Gamboa Gabriela, Fabbri Julia, Ceballos Laura, Sanchez Bruni Sergio, Alvarez Luis I, Allemandi Daniel, Benoit Jean Pierre, Palma Santiago D, Elissondo María C
Laboratorio de Zoonosis Parasitaria, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina; Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina.
Acta Trop. 2015 Dec;152:185-194. doi: 10.1016/j.actatropica.2015.09.016. Epub 2015 Sep 26.
Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE.
因使用阿苯达唑(ABZ)对囊性棘球蚴病(CE)进行药物治疗失败,主要与药物吸收率低有关,这导致血浆和棘球蚴囊肿中的药物水平较低。脂质纳米囊(LNCs)是设计用于包裹亲脂性药物(如ABZ)的纳米载体。当前工作的目标是:(i)在感染细粒棘球绦虫的小鼠中,将ABZ制成ABZ-脂质纳米囊(ABZ-LNCs)或ABZ混悬液(ABZ-SUSP)给药后,对血浆和囊肿中的药物暴露情况进行表征;(ii)比较两种ABZ制剂的临床疗效。在接受ABZ-LNC治疗的动物的血浆和囊肿中获得了增强的阿苯达唑亚砜(ABZ-SO)浓度曲线。与口服ABZ-SUSP后观察到的情况相比,口服和皮下给予ABZ-LNC治疗后,血浆和囊肿中的ABZSO暴露量(AUC0-LOQ)显著更高。此外,在接受ABZ-LNC治疗的小鼠囊肿中测得的ABZSO浓度比血浆中检测到的浓度高1.7倍。这种药物可用性的提高与观察到的ABZ-LNCs对小鼠继发性CE疗效的增加相关,而ABZ-SUSP与未治疗的对照组相比没有差异。这种基于新药物技术的策略可能是改善人类CE治疗的一种潜在替代方法。