Abstract
Human immunodeficiency virus (HIV)-infected individuals display an enhanced production of reactive oxygen species (ROS). This reduction of antioxidant capacity in host tissues has been related to the decrease in total levels of ROS scavengers such as glutathione (GSH). Prevention of opportunistic infections due to a weakened immune system is becoming a key strategy along with HIV elimination. Research in these directions is clearly warranted, especially a combination of antiretrovirals and antioxidants to ameliorate oxidative stress, improve intracellular uptake and target viral reservoirs. Hence, we aimed to formulate liposomes loaded with the antiretroviral drug efavirenz (EFA) in the presence of glutathione, as these carriers can be engineered to enhance the ability to reach the target reservoirs. The goal of the present work was to investigate the intracellular uptake of EFA-loaded liposome (with and without GSH) by human monocytic leukemia cells (THP-1 cells) and examine cell viability and ROS scavenging activity. Results obtained provided significant data as follows: (i) treatment with EFA and GSH combination could enhance the uptake and reduce cytotoxicity; (ii) encapsulation of EFA into liposomes increased its levels in the macrophages, which was further enhanced in the presence of GSH; (iii) delivery of EFA in the presence of GSH quenched the intracellular ROS, which was significantly higher when delivered via liposomes. Data revealed that a combination of EFA and GSH encompasses advantages; hence, GSH supplementation could be a safe and cost-effective treatment to slow the development of HIV infection and produce an immune-enhancing effect.
Highlights
Publisher’s Note: MDPI stays neutralAccording to the World Health Organization, at the end of 2020, about 37.7 million (30.2–45.1 million) people were infected with the human immunodeficiency virus (HIV); 680,000 [480,000–1.0 million] people died from HIV-related causes and 1.5 million [1.0–2.0 million] people have acquired HIV [1]
These study findings indicate that macrophages can serve as a genuine target for HIV infection in vivo by sustaining and transmitting HIV infection [59]
GSH in combination could enhance the uptake and reduce cytotoxicity (ii) encapsulation of EFA into liposomes increased its levels in the macrophages further enhanced in the presence of GSH; (iii) co-delivery of EFA + GSH quenched the intracellular reactive oxygen species (ROS), significantly higher when delivered via liposomes
Summary
Publisher’s Note: MDPI stays neutralAccording to the World Health Organization, at the end of 2020, about 37.7 million (30.2–45.1 million) people were infected with the human immunodeficiency virus (HIV); 680,000 [480,000–1.0 million] people died from HIV-related causes and 1.5 million [1.0–2.0 million] people have acquired HIV [1]. Innumerable opportunistic infections associated with HIV infections include Kaposi sarcoma, Pneumocystic pneumonia, Herpes virus and Mycobacterium tuberculosis (M. tb), all of which could result in poor patient survival [3]. These infections flourish due to a compromised immune system, which follows the depletion of CD4+ T cells. Mycobacterial infections have increased due to growing numbers of highly susceptible immunocompromised individuals arising from the AIDS epidemic. Oxidative stress and immunological dysfunction are believed to adversely impact mycobacterial outcomes, resulting in higher risks of disease relapse and mortality and a greater propensity for developing drug-resistant infections [4,5,6,7]. Mycobacterial co-infection is with regard to jurisdictional claims in published maps and institutional affiliations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
