| Autor: |
Permana AD; Department of Pharmaceutics, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia., Paredes AJ; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom., Zanutto FV; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.; Faculty of Pharmaceutical Sciences, University of Campinas, R. Cândido Portinari, 200 - Cidade Universitária, Campinas, SP 13083-871, Brazil., Amir MN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia., Ismail I; Department of Phytochemistry, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia., Bahar MA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia., Sumarheni; Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia., Palma SD; Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, X5000XHUA, Córdoba, Argentina., Donnelly RF; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom. |
| Abstrakt: |
Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus spp., affecting both humans and animals' lives. Current treatment of CE by oral administration of albendazole (ABZ) is hampered by several limitations. The poor aqueous solubility and the rapid metabolism of ABZ in the liver are the main issues, leading to lack of efficacy of the treatment. In the present study, we developed a nanocrystalline (NC) formulation of ABZ to be delivered intradermally using dissolving microneedles (DMNs). The NC formulation was developed using milling in an ultrasmall-scale device. Following several screenings, Pluronic F127 was selected as a suitable stabilizer, producing NCs with around 400 nm in size with narrow particle distribution. The crystallinity of ABZ was maintained as observed by DSC and XRD analysis. The NC approach was able to improve the dissolution percentage of ABZ by approximately three-fold. Furthermore, the incorporation of NCs into DMNs using the combination of poly(vinylpyrrolidone) and poly(vinyl alcohol) formed sharp needles with sufficient mechanical strength and insertion properties. Dermatokinetic studies revealed that >25% of ABZ was localized in the dermis of excised neonatal porcine skin up to 48 h after DMN administration. In in vivo pharmacokinetic studies, the AUC and relative bioavailability values of ABZ delivered by NC-loaded DMNs were found to be significantly higher than those obtained after oral administration of coarse suspension of ABZ or ABZ-NCs, as well as DMNs delivering coarse ABZ as indicated by the relative bioavailability values of >100%. Therefore, the combination approach developed in this study could maintain the systemic circulation of ABZ, which could be possibly caused by avoiding the first-pass metabolism in the liver. This could be beneficial to improve the efficacy of ABZ in CE treatment. |
