Drug Delivery System Targeting CD4⁺ T Cells for HIV-1 Latency Reactivation Towards the Viral Eradication

• Main Authors: Thanapak Jaimalai, Suthasinee Meeroekyai, Nuttee Suree, Panchika Prangkio
• Format: Journal
• Published: 2020
• Subjects: Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85087813051&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/71012
• Institution: Chiang Mai University

© 2020 American Pharmacists Association® Development of a cure for HIV/AIDS has been a great challenge due to the establishment of the HIV-1 viral reservoir, mainly within resting CD4+ memory T cells. As a step towards a cure for HIV, this study aimed to develop an approach that reactivates HIV-1 latently infected cells by employing a drug delivery system using immunoliposomes targeting CD4+ T cells. The immunoliposomes were examined for physicochemical properties and determined for their potential stability. A histone deacetylase (HDAC) inhibitor SAHA was used as a model drug being encapsulated within the immunoliposomes that are conjugated with anti-CD4 antibodies. The immunoliposomes are effectively and specifically taken up by the CD4+ J-Lat 10.6 cells, and significantly less so by the CD4− ACH-2 cells. For HIV-1 latent cell reactivation, SAHA-encapsulated immunoliposomes (SAHA-IL) and SAHA-encapsulated liposomes (SAHA-LP) can reactivate HIV latency as effectively as SAHA compound alone. Additionally, a combination of SAHA-IL and a protein kinase C activator, bryostatin-1, also exhibits a synergistic effect on the reactivation. The developed system thus presents a viable option to become a promising approach for HIV-1 latency reversing treatment, a strategy towards developing a functional cure for HIV.