Adjunctive and long-acting nanoformulated antiretroviral therapies for HIV-associated neurocognitive disorders

Gendelman, Howard E.; Gelbard, Harris A.

doi:10.1097/coh.0000000000000111

Cited by 15 publications

(10 citation statements)

References 57 publications

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“…Data in the literature have been mainly focused on animal infection models of nose-to-brain delivery of ketoconazole in cryptococcal meningoencephalitis [ 7 ] or on adjunctive and long-acting nanoformulated antiretroviral therapies for HIV-associated neurocognitive disorders [ 9 , 45 , 46 ], whereas data regarding bacterial infections are scarce [ 7 ]. NEs described in this study appear suitable to be administered intranasally and indicated potential benefits over other types of delivery systems.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

et al. 2020

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Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

et al. 2020

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“…For instance, nanoparticle-based delivery of doxorubicin in a rodent model of hepatocellular carcinoma was associated with significant reduction in cardiotoxicity associated with the free drug [175]. Similarly, in the last few years, antiretroviral drugs are also being formulated especially for enhanced drug delivery across blood-brain-barrier to treat HIV infection in the brain [176, 177]. CNS bioavailability of antiretroviral drugs like azidothymidine 5’-triphosphate [178] and saquinavir [179] was reported to be significantly higher following their dosing as nanoformulations.…”

Section: Development Of Das Analogs As Novel Therapeuticsmentioning

confidence: 99%

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Rao¹,

Midde²,

Miller³

et al. 2015

CDM

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Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.

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“…As such, improving ART penetration across the BBB remains an important goal. The use of nano-ART (“cell-mediated medication delivery”; reviewed in Gendelman and Gelbard, 2014 ) or the use of intranasal delivery (reviewed in Hanson and Frey, 2007 ), have shown improved efficiency in that regard. The addition to ART of adjunctive therapies targeting the excitotoxicity, inflammatory or anti-oxidant systems is also being explored.…”

Section: Neurotoxicity By Methamphetamine Use and Hiv-1 Infection: Pomentioning

confidence: 99%

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

et al. 2015

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Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood–brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments.

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Adjunctive and long-acting nanoformulated antiretroviral therapies for HIV-associated neurocognitive disorders

Cited by 15 publications

References 57 publications

Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

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