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1.
Int J Biol Macromol ; 280(Pt 3): 135885, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39307507

ABSTRACT

This study focuses on optimizing the delivery of Nelfinavir (NFV), a vital protease inhibitor in antiretroviral therapy, and Epigallocatechin gallate (EGCG), a potent adjunctive anti- human immunodeficiency virus (anti-HIV) agent found in green tea. The challenge lies in NFV's low intrinsic dissolution rate, significant p-gp efflux, and high hepatic metabolism, necessitating frequent and high-dose administration. Our objective was to develop a nanoemulsion loaded with NFV and EGCG to enhance oral delivery, expediting antiretroviral effects for NeuroAIDS treatment. After meticulous excipient screening, we selected Tween 40 as the surfactant and polyethylene glycol 400 (PEG 400) as the co-surfactant. Employing a Quality by Design (QbD) approach with statistical multivariate methods, we optimized the nanoemulsion that exhibited a droplet size of 83.21 nm, polydispersity index (PDI) of 2.289, transmittance of 95.20 %, zeta potential of 1.495 mV, pH of 6.95, refractive index of 1.40, viscosity of 24.00 ± 0.42 mPas, and conductivity of 0.162 µS/cm. Pharmacokinetic studies demonstrated superior in vivo absorption of the optimized nanoemulsion compared to NFV and EGCG suspension. The optimized nanoemulsion showcased higher Cmax of NFV (9.75 ± 1.23 µg/mL) and EGCG (27.7 ± 1.22 µg/mL) in the brain, along with NFV (26.44 ± 1.44 µg/mL) and EGCG (313.20 ± 5.53 µg/mL) in the plasma. This study advocates for the potential of NFV and EGCG-loaded nanoemulsion in combination antiretroviral therapy (cART) for effective NeuroAIDS management.

2.
FEBS Lett ; 598(15): 1919-1936, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38789398

ABSTRACT

Nanotechnology offers promising avenues for enhancing drug delivery systems, particularly in HIV-1 treatment. This study investigates a nanoemulsified formulation combining epigallocatechin gallate (EGCG) with dolutegravir (DTG) for managing HIV-1 infection. The combinatorial interaction between EGCG and DTG was explored through cellular, enzymatic, and molecular studies. In vitro assays demonstrated the potential of a dual drug-loaded nanoemulsion, NE-DTG-EGCG, in inhibiting HIV-1 replication, with EGCG serving as a supplementary treatment containing DTG. In silico molecular interaction studies highlighted EGCG's multifaceted inhibitory potential against HIV-1 integrase and reverse transcriptase enzymes. Further investigations are needed to validate the formulation's efficacy across diverse contexts. Overall, by integrating nanotechnology into drug delivery systems, this study represents a significant advancement in managing HIV-1 infection.


Subject(s)
Catechin , HIV-1 , Heterocyclic Compounds, 3-Ring , Oxazines , Piperazines , Pyridones , Virus Replication , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/chemistry , Pyridones/pharmacology , Pyridones/chemistry , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/chemistry , Piperazines/pharmacology , Piperazines/chemistry , Oxazines/pharmacology , HIV-1/drug effects , Humans , Virus Replication/drug effects , Emulsions , HIV Integrase/metabolism , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/chemistry , Anti-HIV Agents/pharmacology , Anti-HIV Agents/chemistry , Nanoparticles/chemistry , HIV Infections/drug therapy , HIV Infections/virology
3.
Healthcare (Basel) ; 12(4)2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38391789

ABSTRACT

India continues to grapple with a significant burden of HIV infections. Despite notable progress in prevention and treatment efforts, multiple challenges, such as high-risk populations, inadequate testing facilities, and limited access to healthcare in remote areas, persist. Though the Government of India offers HIV-1 plasma viral load testing at various medical centers, aiding treatment decisions and monitoring antiretroviral therapy effectiveness, enhancing care for individuals living with HIV under the National AIDS Control Program (NACP), the nation's large population and diverse demographics further complicate its outreach and response. Hence, strategic interventions and alternative methods of testing remain crucial to curbing HIV transmission and improving the quality of life for those affected. Dried blood spot (DBS) sampling has emerged as a convenient and cost-effective alternative for HIV-1 viral load testing, revolutionizing the landscape of diagnostic and monitoring strategies for HIV infection. Though the plasma-based viral load remains the gold standard for monitoring HIV-1, DBS-based HIV-1 viral load testing holds immense promise for improving access to care, particularly in resource-limited settings where traditional plasma-based methods may be logistically challenging. DBS entails the collection of a small volume of blood onto filter paper, followed by drying and storage. This approach offers numerous advantages, including simplified sample collection, transportation, and storage, reducing the need for cold-chain logistics. Recent studies have demonstrated the feasibility and accuracy of DBS-based HIV-1 viral load testing, revealing a strong correlation between DBS and plasma measurements. Its implementation can enhance the early detection of treatment failure, guide therapeutic decisions, and ultimately contribute to better clinical outcomes for HIV-infected individuals. Hence, this review explores the principles, advancements, feasibility, and implications of DBS-based HIV-1 viral load testing.

4.
Ther Adv Vaccines Immunother ; 10: 25151355221106104, 2022.
Article in English | MEDLINE | ID: mdl-35832725

ABSTRACT

Approximately 2.3 million people are suffering from human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection worldwide. Faster disease progression and increased mortality rates during the HIV/HCV co-infection have become global health concerns. Effective therapeutics against co-infection and complete infection eradication has become a mandatory requirement. The study of small non-coding RNAs in cellular processes and viral infection has so far been beneficial in various terms. Currently, microRNAs are an influential candidate for disease diagnosis and treatment. Dysregulation in miRNA expression can lead to unfavorable outcomes; hence, this exact inevitable nature has made various studies a focal point. A considerable improvement in comprehending HIV and HCV mono-infection pathogenesis is seen using miRNAs. The prominent reason behind HIV/HCV co-infection is seen to be their standard route of transmission, while some pieces of evidence also suspect viral interplay between having a role in increased viral infection. This review highlights the involvement of microRNAs in HIV/HCV co-infection, along with their contribution in HIV mono- and HCV mono-infection. We also discuss miRNAs that carry the potentiality of becoming a biomarker for viral infection and early disease progression.

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