Palombo M S, Singh Y, Sinko P J
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd., Piscataway, NJ 08854-8022, USA.
J Drug Deliv Sci Technol. 2009;19(1):3-14. doi: 10.1016/s1773-2247(09)50001-9.
Despite the wide variety of highly potent anti-HIV drugs that have been developed and made available in clinical practice over the years, eradication of HIV infection has not been achieved. Currently, HIV infection and AIDS are thought to be chronically treatable. HIV attacks host immune cells namely macrophages and CD4(+)T-cells and sequesters itself into sanctuary and reservoir sites such as the lymphoid tissues, testes, and brain. Initial drug delivery efforts with prodrugs and drug conjugates focused on improving the physicochemical (i.e. solubility), biopharmaceutic (i.e. absorption, metabolism), and pharmacokinetic (i.e. blood concentrations) properties of the parent drugs. Eradicating HIV, however, will require advanced drug delivery approaches in order to access and maintain effective drug concentrations for prolonged periods of time in sanctuary sites. The current review discusses prodrug/conjugate efforts, clinical successes and describes drug delivery challenges and approaches for eradicating HIV infection.
尽管多年来已开发出多种高效抗艾滋病毒药物并应用于临床实践，但尚未实现艾滋病毒感染的根除。目前，艾滋病毒感染和艾滋病被认为是可长期治疗的。艾滋病毒攻击宿主免疫细胞，即巨噬细胞和CD4(+)T细胞，并将自身隐匿于诸如淋巴组织、睾丸和大脑等庇护所和储存部位。最初使用前药和药物缀合物的给药努力集中在改善母体药物的物理化学性质（即溶解度）、生物药剂学性质（即吸收、代谢）和药代动力学性质（即血药浓度）。然而，根除艾滋病毒将需要先进的给药方法，以便在庇护所部位长时间达到并维持有效的药物浓度。本综述讨论了前药/缀合物的研究工作、临床成果，并描述了根除艾滋病毒感染的给药挑战和方法。
