Lina Zhou, Sandip Godse, Namita Sinha, Dejian Ma, Golnoush Mirzahosseini, Mohd Salman, Paul Pulliam, Chalet Tan, Udai P Singh, Tauheed Ishrat, Harry Kochat, Santosh Kumar
{"title":"细胞外囊泡-脂质体-达那韦制剂治疗HIV神经发病机制。","authors":"Lina Zhou, Sandip Godse, Namita Sinha, Dejian Ma, Golnoush Mirzahosseini, Mohd Salman, Paul Pulliam, Chalet Tan, Udai P Singh, Tauheed Ishrat, Harry Kochat, Santosh Kumar","doi":"10.1021/acsanm.4c04637","DOIUrl":null,"url":null,"abstract":"<p><p>This study evaluates the efficacy of an extracellular vesicles-liposome-darunavir (EV-Lip-DRV) formulation for the treatment of HIV neuropathogenesis, including neurocognitive disorders. The EV-Lip-DRV formulation was developed through a process involving thin-film hydration and extrusion, followed by ultrafiltration to remove unloaded DRV. The encapsulation efficiency was found to be 41.75 ± 2.19%, with a particle size of ∼189 nm and zeta potential of ∼-7.8 mV. The hemocompatibility test confirmed the safety of the formulation for red blood cells, while drug release profiles demonstrated a sustained release of DRV within 24 h. Our <i>in vitro</i> experiment showed that EV-Lip-DRV significantly reduces HIV replication in U1 macrophages and alters the pro-inflammatory cytokine and chemokine levels. Pharmacokinetic studies in C57BL/6 mice via intranasal administration revealed significantly enhanced drug delivery in the brain, relative to systemic circulation and other peripheral organs. Behavioral studies using EcoHIV-infected mice indicated significant improvements in HIV-associated impaired cognitive and motor functions when treated with the EV-Lip-DRV formulation compared to those with DRV alone. Furthermore, analysis of brain tissues from these mice showed significantly reduced HIV-associated inflammatory response, oxidative stress, DNA damage, and neuronal damage in EV-Lip-DRV as compared with DRV alone. Taken together, these findings suggest that EV-Lip is a promising vehicle for enhancing the delivery of antiretroviral drugs to the brain, potentially ameliorating symptoms associated with HIV neuropathogenesis and improving overall outcomes in HIV treatment.</p>","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":"8 14","pages":"6857-6876"},"PeriodicalIF":5.5000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997951/pdf/","citationCount":"0","resultStr":"{\"title\":\"Extracellular Vesicle-Liposome-Darunavir Formulation for the Treatment of HIV Neuropathogenesis.\",\"authors\":\"Lina Zhou, Sandip Godse, Namita Sinha, Dejian Ma, Golnoush Mirzahosseini, Mohd Salman, Paul Pulliam, Chalet Tan, Udai P Singh, Tauheed Ishrat, Harry Kochat, Santosh Kumar\",\"doi\":\"10.1021/acsanm.4c04637\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study evaluates the efficacy of an extracellular vesicles-liposome-darunavir (EV-Lip-DRV) formulation for the treatment of HIV neuropathogenesis, including neurocognitive disorders. The EV-Lip-DRV formulation was developed through a process involving thin-film hydration and extrusion, followed by ultrafiltration to remove unloaded DRV. The encapsulation efficiency was found to be 41.75 ± 2.19%, with a particle size of ∼189 nm and zeta potential of ∼-7.8 mV. The hemocompatibility test confirmed the safety of the formulation for red blood cells, while drug release profiles demonstrated a sustained release of DRV within 24 h. Our <i>in vitro</i> experiment showed that EV-Lip-DRV significantly reduces HIV replication in U1 macrophages and alters the pro-inflammatory cytokine and chemokine levels. Pharmacokinetic studies in C57BL/6 mice via intranasal administration revealed significantly enhanced drug delivery in the brain, relative to systemic circulation and other peripheral organs. Behavioral studies using EcoHIV-infected mice indicated significant improvements in HIV-associated impaired cognitive and motor functions when treated with the EV-Lip-DRV formulation compared to those with DRV alone. Furthermore, analysis of brain tissues from these mice showed significantly reduced HIV-associated inflammatory response, oxidative stress, DNA damage, and neuronal damage in EV-Lip-DRV as compared with DRV alone. 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Extracellular Vesicle-Liposome-Darunavir Formulation for the Treatment of HIV Neuropathogenesis.
This study evaluates the efficacy of an extracellular vesicles-liposome-darunavir (EV-Lip-DRV) formulation for the treatment of HIV neuropathogenesis, including neurocognitive disorders. The EV-Lip-DRV formulation was developed through a process involving thin-film hydration and extrusion, followed by ultrafiltration to remove unloaded DRV. The encapsulation efficiency was found to be 41.75 ± 2.19%, with a particle size of ∼189 nm and zeta potential of ∼-7.8 mV. The hemocompatibility test confirmed the safety of the formulation for red blood cells, while drug release profiles demonstrated a sustained release of DRV within 24 h. Our in vitro experiment showed that EV-Lip-DRV significantly reduces HIV replication in U1 macrophages and alters the pro-inflammatory cytokine and chemokine levels. Pharmacokinetic studies in C57BL/6 mice via intranasal administration revealed significantly enhanced drug delivery in the brain, relative to systemic circulation and other peripheral organs. Behavioral studies using EcoHIV-infected mice indicated significant improvements in HIV-associated impaired cognitive and motor functions when treated with the EV-Lip-DRV formulation compared to those with DRV alone. Furthermore, analysis of brain tissues from these mice showed significantly reduced HIV-associated inflammatory response, oxidative stress, DNA damage, and neuronal damage in EV-Lip-DRV as compared with DRV alone. Taken together, these findings suggest that EV-Lip is a promising vehicle for enhancing the delivery of antiretroviral drugs to the brain, potentially ameliorating symptoms associated with HIV neuropathogenesis and improving overall outcomes in HIV treatment.
期刊介绍:
ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.