School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University Under Section 3 of UGC Act - 1956, Elite Status and Center of Excellence - Govt. of Maharashtra, TEQIP Phase III Funded, Mumbai 400019, India.
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
Eur J Pharm Biopharm. 2021 Aug;165:41-51. doi: 10.1016/j.ejpb.2021.04.024. Epub 2021 May 8.
A key challenge of HIV treatment with multiple antiretroviral drugs is patient adherence. Thus, there is an urgent need for long-acting depot systems for delivering drugs over an extended duration. Although the parenteral route is preferred for depot systems, it is associated with obvious drawbacks, such as painful injections, potentially-contaminated sharps waste, and the necessity of trained healthcare personnel for administration. Amongst a small number of alternatives in development microneedles are versatile delivery systems enabling systemic drug delivery and potentially improving patient adherence due to their capacity for self-administration. We have developed dissolving microneedle (DMNs) embedded with etravirine nanosuspension (ETR NS) as a long-acting HIV therapy to improve patient adherence. The ETR NS prepared by sonoprecipitation yielded particle sizes of 764 ± 96.2 nm, polydispersity indices of of 0.23 ± 0.02, and zeta potentials of -19.75 ± 0.55 mV. The DMNs loaded with ETR NS demonstrated 12.84 ± 1.33% ETR deposition in ex-vivo neonatal porcine skin after 6 h application. In in vivo rat pharmacokinetic studies, the Cmax exhibited by DMNs loaded with ETR powder and ETR NS were 158 ± 10 ng/mL and 177 ± 30 ng/mL, respectively. DMN groups revealed a higher t, Tmax, and mean residence time compared to intravenous ETR solutions, suggesting the long-acting potential of etravirine delivered intradermally using DMNs.
用多种抗逆转录病毒药物治疗 HIV 的一个关键挑战是患者的依从性。因此，迫切需要能够延长药物释放时间的长效储库系统。虽然注射给药是储库系统的首选途径，但它存在明显的缺点，如疼痛的注射、潜在污染的锐器废物以及需要经过培训的医疗保健人员进行给药。在少数正在开发的替代方法中，微针是多功能的给药系统，能够实现全身药物递送，并由于其自我给药的能力，有潜力提高患者的依从性。我们已经开发了包埋依托昔韦纳米混悬剂（ETR NS）的可溶解微针（DMNs）作为长效 HIV 治疗方法，以提高患者的依从性。超声沉淀法制备的 ETR NS 的粒径为 764 ± 96.2nm，多分散指数为 0.23 ± 0.02，zeta 电位为-19.75 ± 0.55mV。在离体新生猪皮中，经过 6h 应用后，负载 ETR NS 的 DMNs 中 ETR 的沉积量为 12.84 ± 1.33%。在体内大鼠药代动力学研究中，负载依托昔韦粉末和 ETR NS 的 DMNs 的 Cmax 分别为 158 ± 10ng/mL 和 177 ± 30ng/mL。DMN 组与静脉内 ETR 溶液相比，t、Tmax 和平均停留时间更高，表明依托昔韦经皮给药使用 DMNs 具有长效潜力。
