a The Institute for Drug Research of the School of Pharmacy , The Hebrew University of Jerusalem , Jerusalem , Israel.
b Department of Pathology and Immunology , The Lautenberg Center for General and Tumor Immunology, The Hebrew University of Jerusalem , Jerusalem , Israel.
J Drug Target. 2019 Jun-Jul;27(5-6):590-600. doi: 10.1080/1061186X.2018.1552275. Epub 2018 Dec 18.
Lopinavir (LPV), an efficient drug for HIV infection treatment, was incorporated into biodegradable PLGA nanocapsules (NCs) embedded in microparticles (MCPs) using the spray-drying technique in an attempt to bypass the P-gp efflux and protect the drug from CYP3A pre-systemic metabolism without ritonavir (RTV). SEM observations confirmed the formation of NCs and their entrapment in the MCPs. LPV-loaded NCs and free LPV were released from the MCPs at pH of 7.4 as evidenced by in vitro release studies. Results obtained from rat studies showed a two-fold higher bioavailability of LPV following oral administration of the optimal formulation than Kaletra, the marketed drug, showing that when properly entrapped, LPV can be effectively protected from CYP degradation in the gut as well as from the liver following systemic absorption. It was also shown that serum derived from rats following LPV oral administration in two formulations and Kaletra significantly decreased the multiplication of HIV-1 in cultured SupT1 cells. Furthermore, the LPV formulations markedly restricted the titre of infectious HIV-1 production compared with Kaletra confirming the improved antiviral activity of LPV delivered in the rat blood circulation by the nanocapsules embedded in microparticle formulations.
洛匹那韦（LPV）是一种有效的 HIV 感染治疗药物，它被包裹在微球（MCPs）中的可生物降解的 PLGA 纳米胶囊（NCs）中，使用喷雾干燥技术来绕过 P-糖蛋白外排并保护药物免受 CYP3A 预系统性代谢，而无需利托那韦（RTV）。SEM 观察证实了 NCs 的形成及其在 MCPs 中的包封。体外释放研究表明，LPV 负载的 NCs 和游离 LPV 可在 pH 7.4 时从 MCPs 中释放。大鼠研究结果表明，与市售药物 Kaletra 相比，口服最佳制剂后 LPV 的生物利用度提高了两倍，这表明当适当包封时，LPV 可以有效地防止在肠道中被 CYP 降解，以及在系统吸收后被肝脏降解。研究还表明，两种制剂和 Kaletra 口服 LPV 后从大鼠血清中显著降低了培养的 SupT1 细胞中 HIV-1 的繁殖。此外，与 Kaletra 相比，LPV 制剂显著限制了感染性 HIV-1 产生的滴度，这证实了通过微球嵌入纳米胶囊制剂在大鼠血液循环中传递的 LPV 的抗病毒活性得到了改善。
