Investigation of Molecular Properties of Antiretroviral Agents to Enhance CNS Penetration Abilities for the Treatment of Cognitive Impairment in HIV-Associated Neurocognitive Disorder

Danta, Chhanda Charan; Piplani, Poonam

doi:10.1021/acschemneuro.0c00329

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Other examples are so-called molecular umbrellas, capable of transporting hydrophilic cargo through lipid bilayers [595][596][597] or hydrophobic cargo through aqueous solution [598]. In a similar spirit, the use of conjugated antioxidants with antiretroviral drugs has been proposed to increase drug penetration into the central nervous system [599]. Additionally, peptides, including antimicrobial peptides, were proposed as an effective enhancer [600,601].…”

Section: Translocation Through the Membranementioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: Translocation Through the Membranementioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…ARV drugs may also be expelled from CNS at the BBB level by efflux transporters like glycoprotein P (P-gp) [ 47 ]. Simultaneously, the inflammatory response induced by HIV infection of the CNS causes permeability increase of the BBB and plays an important role in neuropathogenesis [ 47 , 48 ].…”

Section: Arv Agents: Mechanism Of Action and Limitationsmentioning

confidence: 99%

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

et al. 2021

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Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed.

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“…ARV drugs may also be expelled from CNS at the BBB level by efflux transporters like glycoprotein P (P-gp) [47]. Simultaneously, the inflammatory response induced by HIV infection of the CNS causes permeability increase of the BBB and plays an important role in neuropathogenesis [47,48].…”

Section: Figurementioning

confidence: 99%

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

Faria¹,

Lopes²,

Neves³

et al. 2021

Preprint

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Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life and poor penetration into HIV reservoir sites, which contribute to the sub-optimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review focus on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARVs to overcome biological barriers upon administration. Furthermore, a correlation of these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference delivery for the treatment of HIV infections were also discussed.

show abstract

Investigation of Molecular Properties of Antiretroviral Agents to Enhance CNS Penetration Abilities for the Treatment of Cognitive Impairment in HIV-Associated Neurocognitive Disorder

Cited by 3 publications

References 6 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

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