title: Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.
abstract: 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.
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: antgnelson@gmail.com.
authors: Antoinette G
authors: AG
authors: Nelson
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: xzhang@rci.rutgers.edu.
authors: Xiaoping
authors: X
authors: Zhang
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: ganapaus@rci.rutgers.edu.
authors: Usha
authors: U
authors: Ganapathi
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: zoltan@rci.rutgers.edu.
authors: Zoltan
authors: Z
authors: Szekely
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: flex@jhmi.edu.
authors: Charles W
authors: CW
authors: Flexner
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: aowen@liverpool.ac.uk.
authors: Andrew
authors: A
authors: Owen
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: sinko@rutgers.edu.
authors: Patrick J
authors: PJ
authors: Sinko
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000517:prevention & control; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D065129:Pre-Exposure Prophylaxis
chemical_list: D019380:Anti-HIV Agents
keywords: Antiretroviral drugs (ARV); Drug delivery targeting; HIV/AIDS; Long-acting/extended-release (LA/ER); Nanomedicine; Nanotechnology; Pre-exposure prophylaxis (PrEP)