ROS Chronicles in HIV Infection: Genesis of Oxidative Stress, Associated Pathologies, and Therapeutic Strategies DOI Creative Commons

R Harshithkumar,

Prachibahen Shah,

Pratiksha Jadaun

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 8852 - 8873

Published: Aug. 14, 2024

Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role pathogenesis of HIV infection is associated with several comorbidities HIV-infected individuals. ROS, generated both naturally during mitochondrial metabolism response trigger host antiviral responses also promote viral replication. While multifaceted ROS pathophysiology clearly need more investigation, this review paper unravels mechanisms generation context infections, offering insights into protein-mediated antiretroviral therapy-generated OS. Though protein Tat significantly attributed endogenous increase post infection, sums up contribution other proteins HIV-mediated elicitation ROS. Given investigations recognizing significant onset progression diverse pathologies, explores function mediation an array pathologies retroviral therapy. patients observed disruption antioxidant defense system, therapy gaining focus potential therapeutic intervention well discussed. scenario, further exploratory studies imperative identifying alternative strategies could mitigate toxicities ART-induced

Language: Английский

Nanoparticles as delivery vehicles for antiviral therapeutic drugs DOI Creative Commons

Alexander Maus,

Lia Strait,

Donghui Zhu

et al.

Engineered Regeneration, Journal Year: 2021, Volume and Issue: 2, P. 31 - 46

Published: Jan. 1, 2021

With the ongoing COVID-19 pandemic still escalating, many researchers are turning to nanotechnology as a method of treatment not only for this pandemic, but in preparation pandemics future. Given both wide variety biomaterials at their disposal and recent rise nanotechnology, scientists now have means release distribute therapeutic drugs ways. Such permits medical professionals ability choose methods that would provide best methodologies viral ailment they attempting remedy. This integrative review discusses context previous pandemics, pathogenesis, issues associated with current state antiviral delivery systems, numerous used purpose, further information regarding global pandemic.

Language: Английский

Citations

95
Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation DOI Creative Commons
Suyash Deodhar, Brady Sillman, Aditya N. Bade

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 9, 2022

Abstract Ultra-long-acting integrase strand transfer inhibitors were created by screening a library of monomeric and dimeric dolutegravir (DTG) prodrug nanoformulations. This led to an 18-carbon chain modified ester nanocrystal (coined NM2DTG) with the potential sustain yearly dosing. Here, we show that physiochemical pharmacokinetic (PK) formulation properties facilitate slow drug release from tissue macrophage depot stores at muscle injection site adjacent lymphoid tissues following single parenteral injection. Significant plasma levels are recorded up year Tissue sites for hydrolysis dependent on dissolution release, drug-depot volume, perfusion, cell-tissue pH. Each affect extended NM2DTG apparent half-life PK parameters. The product can impact therapeutic adherence, tolerability, access widely used inhibitor in both resource limited rich settings reduce HIV-1 transmission achieve optimal treatment outcomes.

Language: Английский

Citations

40
Self-assembled lipid–prodrug nanoparticles DOI
Patrick Couvreur, Sinda Lepêtre‐Mouelhi, Elisa Garbayo

et al.

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(10), P. 749 - 768

Published: June 28, 2023

Language: Английский

Citations

26
Advances in long-acting slow effective release antiretroviral therapies for treatment and prevention of HIV infection DOI Creative Commons
Mohammad Ullah Nayan, Brady Sillman, Mahmudul Hasan

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 115009 - 115009

Published: July 12, 2023

Adherence to daily oral antiretroviral therapy (ART) is a barrier both treatment and prevention of human immunodeficiency virus (HIV) infection. To overcome limitations life-long regimen adherence, long-acting (LA) injectable (ARV) drugs, nanoformulations, implants, vaginal rings, microarray patches, ultra-long-acting (ULA) prodrugs are now available or in development. These medicines enable persons who at risk for HIV infection be treated with simplified ART regimens. First-generation LA cabotegravir, rilpivirine, lenacapavir injectables dapivirine ring use. However, each remains limited by existing dosing intervals, ease administration, difficulties finding drug partners. ULA regimens provide an answer, but date, such next-generation formulations remain Establishing the niche will require affirmation extended dosing, improved access, reduced injection volumes, pharmacokinetic profiles, selections combination treatments, synchronization healthcare support. Based on needs, this review highlights recent pharmacological advances future perspective. While first-generation ARTs care, they far from ideal meeting patient needs. medicines, advanced preclinical development, may close gaps toward broader usage options.

Language: Английский

Citations

25
Carrier‐Free, Amorphous Verteporfin Nanodrug for Enhanced Photodynamic Cancer Therapy and Brain Drug Delivery DOI Creative Commons
John A. Quinlan, Collin T. Inglut, Payal Srivastava

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)

Published: March 6, 2024

Abstract Glioblastoma (GBM) is hard to treat due cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence nearly universal even after surgery, chemotherapy, radiation. Photodynamic therapy (PDT) involves photosensitizer administration followed by light activation generate reactive oxygen species at tumor sites, thereby killing cells or inducing biological changes. PDT can ablate unresectable GBM sensitize tumors chemotherapy. Verteporfin (VP) a promising that relies on liposomal carriers for clinical use. While lipids increase VP's solubility, they also reduce intracellular accumulation. Here, pure‐drug nanoformulation of VP, termed “NanoVP”, eliminating the need lipids, excipients, stabilizers reported. NanoVP has tunable size (65–150 nm) 1500‐fold higher loading capacity than VP. shows 2‐fold in uptake superior efficacy compared In mouse models, NanoVP‐PDT improved control extended animal survival, outperforming VP 5‐aminolevulinic acid (5‐ALA). Moreover, low‐dose safely open blood‐brain barrier, increasing accumulation rat brains 5.5‐fold 5‐ALA. new formulation potential facilitate GBM.

Language: Английский

Citations

10
Ultra-long-acting removable drug delivery system for HIV treatment and prevention DOI Creative Commons
Martina Kovářová, S. Rahima Benhabbour,

Ivana Massud

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Oct. 2, 2018

Abstract Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations antiretrovirals (ARVs) represent a viable alternative improve adherence HIV/AIDS and prevention. However, LA-ARV currently clinical trials cannot be removed after administration even if adverse events occur. Here we show ultra-LA removable system that delivers drug for up 9 months can safely stop delivery. We use two pre-clinical models HIV transmission treatment, non-human primates (NHP) humanized BLT (bone marrow/liver/thymus) mice single dose subcutaneously administered dolutegravir effectively both suppression viremia protection from multiple high-dose vaginal challenges mice. This approach represents potentially effective strategy delivery with possible therapeutic applications.

Language: Английский

Citations

80
Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition DOI Creative Commons
Alan Engelman

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(41), P. 15137 - 15157

Published: Aug. 30, 2019

Antiretroviral inhibitors that are used to manage HIV infection/AIDS predominantly target three enzymes required for virus replication: reverse transcriptase, protease, and integrase. Although integrase were the last among this group be approved treating people living with HIV, they have since risen forefront of treatment options. Integrase strand transfer (INSTIs) now recommended components frontline drug-switch antiretroviral therapy formulations. catalyzes two successive magnesium-dependent polynucleotidyl transferase reactions, 3' processing transfer, INSTIs tightly bind divalent metal ions viral DNA end after processing, displacing from active site 3'-hydroxyl is activity. second-generation present higher barriers development drug resistance than first-generation compounds, mechanisms underlying these superior barrier profiles incompletely understood. A separate class HIV-1 inhibitors, allosteric (ALLINIs), engage distal enzyme site, namely at binding cellular cofactor lens epithelium-derived growth factor (LEDGF)/p75 helps guide integration into host genes. ALLINIs inhibit replication by inducing hypermultimerization, which precludes genomic RNA perturbs morphogenesis new particles. not yet human use, provide important probes can investigate link between particle morphogenesis. Herein, I review retroviral as well promises challenges using HIV/AIDS management.

Language: Английский

Citations

71
A high-resolution growth series ofTyrannosaurus rexobtained from multiple lines of evidence DOI Creative Commons
Thomas D. Carr

PeerJ, Journal Year: 2020, Volume and Issue: 8, P. e9192 - e9192

Published: June 4, 2020

Background During the growth of complex multicellular organisms, chronological age, size and morphology change together in a hierarchical coordinated pattern. Among extinct species, Tyrannosaurus rex has received repeated attention through quantitative analyses relative maturity age. Its series shows an extreme transformation from shallow skulls juveniles to deep adults along with reduction tooth count, its curve that T. had high rate contrast closest relatives. However, separately, these sets data provide incomplete picture congruence between size, this exemplar species. The goal work is analyze using cladistic analysis produce single hypothesis includes all relevant data. Methods three axes were analyzed analysis, based on set 1,850 morphological characters 44 specimens. was run TNT v.1.5 under New Technology search followed by Traditional search. Correlation tests IBM SPSS Statistics v. 24.0.0.0. Results An initial included specimens recovered 50 multiple most parsimonious ontograms identified 13 wildcard without tree (i.e., ontogram) 3,053 steps. ontogram composed 21 stages, but first third are supported unambiguously optimized synontomorphies. ontogeny can be divided into five discrete categories diagnosed morphology, and, part, (uninformative among adults). topology transition skull shape occurred 15 years immediate relatives exceeded 15th 18th years. Although congruent subadults, not seen adults; for example, one least mature (RSM 2523.8) also largest massive example number changes at subadults exhibits secondary metamorphosis, analogous abrupt ontogenetic sexual teleosts. These results point comparison testing mass, as well integrating previous functional rigorous framework. Comparison those outgroup taxa clarifies trends inherited common ancestor Archosauriformes.

Language: Английский

Citations

69
Recent advances in long-acting nanoformulations for delivery of antiretroviral drugs DOI

Dhanashree H. Surve,

Anil B. Jindal

Journal of Controlled Release, Journal Year: 2020, Volume and Issue: 324, P. 379 - 404

Published: May 24, 2020

Language: Английский

Citations

56
Long-acting approaches for delivery of antiretroviral drugs for prevention and treatment of HIV: a review of recent research DOI
Denise Cobb, Nathan Smith, Benson Edagwa

et al.

Expert Opinion on Drug Delivery, Journal Year: 2020, Volume and Issue: 17(9), P. 1227 - 1238

Published: June 17, 2020

Introduction Despite significant advances in treatment and prevention of HIV-1 infection, poor adherence to daily combination antiretroviral therapy (ART) regimens remains a major obstacle toward achieving sustained viral suppression prevention. Adherence ART could also be compromised by adverse drug reactions societal factors that limit access therapy. Therefore, medicines aim improve limiting side effects, frequency dosing socially acceptable are becoming more attractive.Areas covered This review highlights recent challenges the development long-acting delivery strategies for HIV treatment. Approaches extended oral transdermal deliveries, microbicides, broadly neutralizing antibodies, implantable injectable deliveries reviewed.Expert opinion Emerging approaches on therapies antibody technologies currently at various stages development. Such efforts, if successful become accepted clinicians users, will provide newer simpler options infection.

Language: Английский

Citations

52