A5018546819- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Lanthanide and Transition Metal Complexes
- Advanced MRI Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Nanoparticle-Based Drug Delivery
- Advanced Neuroimaging Techniques and Applications
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- MRI in cancer diagnosis
- Tryptophan and brain disorders
- Trace Elements in Health
- Magnetic Properties and Synthesis of Ferrites
- Pregnancy and Medication Impact
- vaccines and immunoinformatics approaches
- Advanced biosensing and bioanalysis techniques
- Infectious Encephalopathies and Encephalitis
- Cannabis and Cannabinoid Research
- Parkinson's Disease Mechanisms and Treatments
- Click Chemistry and Applications
University of Nebraska Medical Center
2016-2025
Abstract Elimination of HIV-1 requires clearance and removal integrated proviral DNA from infected cells tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) CRISPR-Cas9 demonstrate viral in latent infectious reservoirs humanized mice. subgenomic fragments, spanning the long terminal repeats Gag gene, are excised vivo, resulting elimination DNA; virus is not detected blood, lymphoid tissue, bone marrow brain by nested digital-droplet PCR as well RNAscope...
Abstract Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, long-acting parenteral DTG was created through chemical modification improve treatment outcomes. A hydrophobic lipophilic modified prodrug is encapsulated into poloxamer nanoformulations (NMDTG) characterized by size, shape, polydispersity, stability. Retained intracytoplasmic NMDTG particles...
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...
Abstract Treatment and prevention of human immunodeficiency virus type one (HIV-1) infection was transformed through widespread use antiretroviral therapy (ART). However, ART has limitations in requiring life-long daily adherence. Such have led to the creation long-acting (LA) ART. While nucleoside reverse transcriptase inhibitors (NRTI) remain backbone, best our knowledge, none been converted into LA agents. To these ends, we tenofovir (TFV) surfactant stabilized aqueous prodrug...
Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell tissue depots. To this end, ART nanoparticles target folic acid (FA) receptor permit cell-based drug depots were examined using pharmacokinetic pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased bioavailability PD...
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic be made into nanocarrier-encased prodrugs, nanocarrier encasement must boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides function by affecting autophagy. Here, we...
Abstract A once every eight-week cabotegravir (CAB) long-acting parenteral is more effective than daily oral emtricitabine and tenofovir disoproxil fumarate in preventing human immunodeficiency virus type one (HIV-1) transmission. Extending CAB dosing to a yearly injectable advances efforts for the elimination of viral Here we report rigor, reproducibility mechanistic insights year-long injectable. Pharmacokinetic (PK) profiles this nanoformulated prodrug (NM2CAB) are affirmed at three...
Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery human immunodeficiency virus cell tissue reservoirs. In an effort LASER ART development, "multimodal imaging theranostic nanoprobes" were created. These allow combined bioimaging, pharmacokinetics biodistribution tests in animal models.
Abstract Objectives Anti-retroviral therapy (ART) drastically improves human immunodeficiency virus type 1 (HIV-1) outcomes, but may induce adverse neurochemical changes. Interactive effects of ART with recreational drugs are unknown. Notably, people living HIV-1 (PLWH) smoke at twice the rate general population and more prone to tobacco-linked illness. Thus, chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) was employed investigate potential ART-nicotine...
Antiretroviral therapy (ART) restricts human immunodeficiency virus type one (HIV-1) replication and by so doing, improves the quality longevity of life for infected people. Nonetheless, treatment can also lead to adverse clinical outcomes such as drug resistance systemic events. Both could be affected long-acting slow effective release ART. Indeed, maintenance sustained plasma levels, weeks or months, after a single high-level dosing, improve regimen adherence but, at same time, affect...
Purpose: A palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug's half-life, antiretroviral activities and biodistribution. Methods: modified FTC (MFTC) by palmitoyl chloride esterification. MFTC's chemical structure evaluated nuclear magnetic resonance. The created hydrophobic nanocrystals were encased into a poloxamer surfactant pharmacokinetics (PK), biodistribution nanoformulation (NMFTC) assessed. conversion MFTC triphosphates evaluated. Results: coated with...
Dolutegravir (DTG) is a first-line antiretroviral drug (ARV) used in combination therapy for the treatment of human immunodeficiency virus type-1 (HIV-1) infection. The effective, safe, and well tolerated. Nonetheless, concerns have recently emerged its usage pregnant women or those child-bearing age. Notably, DTG-based ARV regimens been linked to birth defects seen as consequence periconceptional usages. To this end, uncovering an underlying mechanism DTG-associated adverse fetal...
Single N<bold>M3ABC</bold>treatment of macrophages produced sustained intracellular carbovir-triphosphate and antiretroviral activities for up to 30 days.
Antiretroviral therapy (ART) has improved the quality of life in patients infected with HIV-1. However, complete viral suppression within anatomical compartments remains unattainable. This is complicated by adverse side effects and poor adherence to lifelong leading emergence drug resistance. Thus, there an immediate need for cellular tissue-targeted long-acting (LA) ART formulations. Herein, we describe two LA prodrug formulations darunavir (DRV), a potent antiretroviral protease inhibitor....