Nelson Antoinette G, Zhang Xiaoping, Ganapathi Usha, Szekely Zoltan, Flexner Charles W, Owen Andrew, Sinko Patrick J
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
J Control Release. 2015 Dec 10;219:669-680. doi: 10.1016/j.jconrel.2015.08.042. Epub 2015 Aug 24.
The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.
2016年将成为一个重要的里程碑——首例报告的艾滋病毒/艾滋病病例35周年。抗逆转录病毒疗法（ART），包括高效抗逆转录病毒疗法（HAART）药物方案，被广泛认为是治疗药物研究中最伟大的成就之一，它已将艾滋病毒感染转变为一种可长期管理的疾病。不幸的是，缺乏广泛的预防措施以及无法从受感染细胞中根除艾滋病毒，凸显了当今仍然存在的重大挑战。展望未来，抗艾滋病毒药物递送（DD）研究至少有三个高度优先目标：（1）防止新的艾滋病毒感染发生；（2）促进功能性治愈，即艾滋病毒存在但身体无需药物就能控制它；（3）根除已有的感染。暴露前预防（PrEP）是预防慢性艾滋病毒感染确立方面向前迈出的重要一步。然而，PrEP的最终成功将取决于能否实现持续的抗逆转录病毒（ARV）组织浓度，并且需要患者严格遵守治疗方案。虽然目前正在研发的第一代长效/缓释（LA/ER）药物递送系统（DDS）显示出相当大的前景，但重大的药物递送治疗和预防挑战依然存在。首先，迫切需要通过靶向来提高细胞特异性，以便在艾滋病毒储存库部位选择性地达到有效药物浓度，从而控制/根除艾滋病毒并减轻全身副作用。此外，需要开发减少ARV药物细胞外排和代谢以延长靶细胞中有效浓度的方法。最后，鉴于目前对艾滋病毒发病机制的了解，下一代抗艾滋病毒DDS需要解决向肠道黏膜和淋巴结的选择性药物递送问题。本综述重点关注药物递送系统技术、关键挑战、机遇、策略以及新的递送系统将有助于朝着预防、功能性治愈并最终根除艾滋病毒感染迈进的方法。
