## 1 Introduction
Among the various approaches to treat HIV infection, strategies targeting viral reservoirs are highly attractive. In this context, the development of delivery systems that can target monocytes/macrophages intracellularly is crucial. Liposomes are the most widely investigated delivery system for phagocyte-targeted therapies, providing advantages such as low immunogenicity, biocompatibility, cell specificity, and drug protection [19]. Lipid-based nanocarriers are reported to hold great promise, with 15 commercial nano lipid medicines as liposomes or lipid nanoparticles, which includes AmBisome(r), DaunoXome(r), Amphotec(r), Fungizone(r), Diprivan(r), Estrasorb(r), Myoccet(r), Visudyne(r), DepoCyt(r), DepoDur(r), Doxii(r),Inflexal(r), Varojbo(r), Abelcet(r)[20; 21; 22]. A recent inclusion is the Pfizer/BioNTech Moderna COVID-19 vaccines used for prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. One of the main reasons for their well-acceptance is because of their structural units, which are generally recognized as safe (GRAS) [23]. The combinational administration of GSH and ARV agents, such as efavirenz, during HIV infection treatment is among one of the most underexplored areas to the best of our knowledge. GSH supplements have been considered useful because they allow patients to alleviate toxic side effects, decrease multidrug resistance (MDR), and provide protection against opportunistic mycobacterial infection. After administration, liposomes are avidly removed from the circulation by the macrophages of the reticuloendothelial system (RES) or mononuclear phagocyte system (MPS) [24]. Apparently, this propensity to be taken up by the macrophages is advantageous in the treatment of diseases such as AIDS, where macrophages harbor infectious HIV [24; 25]. This can be achieved by varying lipid composition to control physicochemical properties such as size and charge [19]. The size of liposomes ranging from 50 to 800 nm in diameter and composed of different types of lipids with neutral, positive, or negative charges have been shown to influence the drug uptake by macrophages [19; 26]. Various examples of therapeutic applications using monocyte/macrophage-targeted liposomes are reported elsewhere. Among them is dideoxycytidine-5-triphosphate for HIV [19]. With efavirenz being a lipophilic molecule and glutathione a hydrophilic molecule, delivery of EFA + GSH can be achieved via liposomes. Liposomes are versatile carriers to encapsulate either/and a hydrophilic or lipophilic molecule, therefore suitable for co-delivery of one or two molecules. Evidence obtained by in vitro studies indicates that short-term treatments with clinically relevant concentrations of EFA reduce cellular proliferation and/or compromise cell viability [9]. Since prevention is becoming a key strategy to eliminate HIV, research in these directions clearly warrants dual drug delivery of antiretrovirals and antioxidants. We hypothesize that delivery of EFA and GSH formulated as liposomal carriers could promote site-specific drug delivery, eliminate viral accumulation, and provide cytoprotective effects in non-infected macrophages (THP-1 cells). Hence, the goal of the present work is 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.