title: Past, Present, and Future Drug Delivery Systems for Antiretrovirals.
abstract: The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has provided improved treatment and prolonged the life expectancy of patients. Moreover, there is growing interest in using ARVs to protect against new infections. Hence, ARVs have emerged as our primary strategy in combating the virus. Unfortunately, several challenges limit the optimal performance of these drugs. First, ARVs often require life-long use and complex dosing regimens. This results in low patient adherence and periods of lapsed treatment manifesting in drug resistance. This has prompted the development of alternate dosage forms such as vaginal rings and long-acting injectables that stand to improve patient adherence. Another problem central to therapeutic failure is the inadequate penetration of drugs into infected tissues. This can lead to incomplete treatment, development of resistance, and viral rebound. Several strategies have been developed to improve drug penetration into these drug-free sanctuaries. These include encapsulation of drugs in nanoparticles, use of pharmacokinetic enhancers, and cell-based drug delivery platforms. In this review, we discuss issues surrounding ARV therapy and their impact on drug efficacy. We also describe various drug delivery-based approaches developed to overcome these issues.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors: Ameya R
authors: AR
authors: Kirtane
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: rlanger@mit.edu.
authors: Robert
authors: R
authors: Langer
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. Electronic address: ctraverso@partners.org.
authors: Giovanni
authors: G
authors: Traverso
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods / Q000639:trends*; D003274:Contraceptive Devices, Female / Q000639:trends; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D005544:Forecasting; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D004304:Dosage Forms
keywords: HIV/AIDS; blood brain barrier; controlled release; global health; injectables; nanoparticles