Nano drug-delivery systems for management of AIDS: liposomes, dendrimers, gold and silver nanoparticles

Abstract

AIDS causes increasing mortality every year. With advancements in nanomedicine, different nanomaterials (NMs) have been applied to treat AIDS and overcome its limitations. Among different NMs, nanoparticles (NPs) can act as nanocarriers due to their enhanced solubility, sustained release, targeting abilities and facilitation of drug-dose reductions. This review discusses recent advancements in therapeutics for AIDS/HIV using various NMs, mainly focused on three classifications: polymeric, liposomal and inorganic NMs. Polymeric dendrimers, polyethylenimine-NPs, poly(lactic-co-glycolic acid)-NPs, chitosan and the use of liposomal-based delivery systems and inorganic NPs, including gold and silver NPs, are explored. Recent advances, current challenges and future perspectives on the use of these NMs for better management of HIV/AIDS are also discussed.

Keywords: antiretroviral therapy; liposomes; nano drug-delivery system; nanomedicine; polymeric and inorganic nanoparticles.

Figure 1.. Applications and properties of dendrimer nanoparticles in HIV therapy.

(A) PAMAM dendrimers, (B) siRNA-loaded PAMAM NPs that silence the HIV mRNA inside host cells to prevent HIV proliferation, (C) peptide-loaded PAMAM NPs that interact with immune cells and induce anti-HIV immune pathways and (D) induction of anti-HIV antibody production in plasma cells. NP: Nanoparticle; PAMAM: Poly(amidoamine).

Figure 2.. Applications and properties of polymeric nanoparticles in HIV therapy.

(A) DNA-loaded PEI NP as a positively charged polymeric NP for DNA-vaccine transfection into dendritic cells; gp120 DNA-vaccine is translated to gp120 proteins inside dendritic cells and presents to CD8⁺ T-cells (cytotoxic T-cells) through MHC-1 molecules. (B) After T-cell activation by dendritic cells, mature T-cells will proliferate and attack HIV-infected cells. (C) ARV free drug will circulate and be cleared in hu-CD3-NSG mice three days after injection. (D) PLGA-ARV polymeric NPs increase drug concentration in hu-CD3-NSG mice and delay its clearance until day 28. ARV: Antiretroviral; NP: Nanoparticle; PEI: Poly(ethyleneimine); PLGA: Poly(lactic-co-glycolic acid).

Figure 3.. Applications and properties of liposomal nanoparticles in HIV therapy.

(A) Targeted liposome NPs loaded with hydrophobic anti-HIV drugs increase the drug entrance into cells in two ways: more targeted and more concentrated drug delivery followed by less blood clearance. (B) Anti-HIV drugs' intestine enzyme degradation is much less, carrying in liposomal vehicles instead of being free delivered. (C) Different administration routes for liposomal formulations due to their stability and biocompatibility. (D) Comparison between drug-release profile of free and liposomal drugs. NP: Nanoparticle.

Figure 4.. Applications and properties of metal nanoparticles in HIV therapy.

(A) Inorganic NPs (AuNPs and AgNPs) loaded with anti-HIV drugs. (B) AuNPs passage through BBB as a promising drug-delivery vehicle. (C) Local aggregation of AgNPs causes reactive oxygen species formation and, subsequently, HIV-infected cell death. (D) AgNPs have antiviral effects through an unknown mechanism by affecting gp120 and gp40 HIV surface molecules. AgNP: Silver nanoparticle; AuNP: Gold nanoparticle; BBB: Blood–brain barrier; NP: Nanoparticle; ROS: Reactive oxygen species;.