Department of Pharmaceutics, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
ACS Appl Mater Interfaces. 2021 Aug 18;13(32):38745-38760. doi: 10.1021/acsami.1c11179. Epub 2021 Aug 5.
Cystic echinococcosis (CE) is a zoonosis caused by 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 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.
包虫病（CE）是一种由 spp.引起的人畜共患病，影响人类和动物的生命。目前，口服阿苯达唑（ABZ）治疗 CE 受到多种限制。ABZ 在水中的溶解度差和在肝脏中的快速代谢是主要问题，导致治疗效果不佳。在本研究中，我们开发了一种 ABZ 的纳米晶体（NC）制剂，通过溶解微针（DMN）皮内给药。NC 制剂是使用超小型设备中的研磨法开发的。经过多次筛选，选择 Pluronic F127 作为合适的稳定剂，产生了大约 400nm 大小且粒径分布较窄的 NC。通过 DSC 和 XRD 分析观察到 ABZ 的结晶度得以维持。NC 方法能够将 ABZ 的溶解百分比提高约三倍。此外，通过将 NC 与聚（乙烯基吡咯烷酮）和聚（聚乙烯醇）结合，将 NC 纳入 DMN 中，形成了具有足够机械强度和插入性能的锋利针。皮肤动力学研究表明，在 DMN 给药后 48 小时内，超过 25%的 ABZ 定位在切除的新生仔猪皮肤的真皮中。在 药代动力学研究中，发现 NC 负载 DMN 给药的 ABZ 的 AUC 和相对生物利用度值明显高于口服粗悬浮 ABZ 或 ABZ-NC 以及 DMN 给药粗 ABZ 后获得的值，相对生物利用度值>100%表明。因此，本研究中开发的联合方法可以维持 ABZ 的全身循环，这可能是由于避免了肝脏中的首过代谢。这可能有助于提高 ABZ 在 CE 治疗中的疗效。
