A5043887039- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- Nanoparticle-Based Drug Delivery
- Forensic Toxicology and Drug Analysis
- Metabolism and Genetic Disorders
- Psychedelics and Drug Studies
- Inhalation and Respiratory Drug Delivery
- Extracellular vesicles in disease
- Cancer, Hypoxia, and Metabolism
- Neurotransmitter Receptor Influence on Behavior
- RNA Interference and Gene Delivery
- Hemoglobinopathies and Related Disorders
- Nanoplatforms for cancer theranostics
- Amino Acid Enzymes and Metabolism
- Advanced Drug Delivery Systems
- Hepatitis B Virus Studies
- Cancer Cells and Metastasis
- Antibiotics Pharmacokinetics and Efficacy
- Pancreatic function and diabetes
- Pregnancy and Medication Impact
- Eicosanoids and Hypertension Pharmacology
- Metabolomics and Mass Spectrometry Studies
- Biochemical and Molecular Research
- Pregnancy and preeclampsia studies
University of North Carolina at Chapel Hill
2016-2025
East Carolina University
2024
University of Helsinki
2022
University of Eastern Finland
2022
Universidade de Santiago de Compostela
2022
Center for Research in Molecular Medicine and Chronic Diseases
2022
Instituto de Investigación Sanitaria de Santiago
2022
Machida Endoscope (Japan)
2022
American Pharmacists Association
2022
Yecuris (United States)
2021
It is commonly observed that hydrophobic molecules alone cannot self-assemble into stable nanoparticles, requiring amphiphilic or ionic materials to support nanoparticle stability and function in vivo. We report herein newly self-assembled nanomedicines through entirely different mechanisms. present proof-of-concept methodology results of our hypothesis disulfide-induced (DSINMs) are promoted stabilized by the insertion a single disulfide bond molecules, order balance competition between...
Uridine-disphosphate glucuronosyl transferase (UGT) enzymes catalyze the formation of glucuronide conjugates phase II metabolism. Methods for absolute quantification UGT1A1 and UGT1A6 were previously established utilizing stable isotope peptide internal standards with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The current method expands upon this by quantifying eight UGT1A isoforms nanobore high-performance chromatography (HPLC) coupled a linear ion trap time-of-flight...
Targeted quantitative proteomics using heavy isotope dilution techniques is increasingly being utilized to quantify proteins, including UGT enzymes, in biological matrices. Here we present a multiplexed method nanoLC-MS/MS and multiple reaction monitoring (MRM) 14 UGT1As UGT2Bs liver Where feasible, employ two or more proteotypic peptides per protein, with only four proteins quantified one peptide. We apply the analysis of library 60 human microsome (HLM) matching S9 samples. Ten isoforms...
Little is known concerning the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) in humans. In addition, potential utilizing stereochemical composition an analyte biological media for forensic purposes requires investigation.The enantiomers MDMA and its demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), present plasma urine extracts were derivatized with (-)-(R)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride analyzed by gas...
In this study, we developed the core-matched nanoemulsions (NEs) functionalized by vitamin E (VE) and tocopherol poly(ethylene glycol)succinate (TPGS) to codeliver hydrophobic hydrophilic drugs, paclitaxel (PTX) 5-fluoroucacil (5-FU), in order achieve synergistic effects overcome PTX resistance a multi-drug-resistant (MDR) human epidermal carcinoma cell line KB-8-5. Antitumor effect of combination therapy based on technology (CMT) was evaluated vitro vivo mice. The NEs showed entrapment...
Renal metabolism by UDP-glucuronosyltransferase (UGT) enzymes is central to the clearance of many drugs. However, significant discrepancies about relative abundance and activity individual UGT in normal kidney prevail among reports, whereas glucuronidation tumoral has not been examined. In this study, we performed an extensive profiling (<i>n</i> = 12) tumor 14) kidneys using targeted mass spectrometry quantification human UGTs. We then correlated protein concentrations with mRNA levels...
Although organic anion transporting polypeptide (OATP)–mediated hepatic uptake is generally conserved between rodents and humans at a gross pharmacokinetic level, the presence of three major OATPs with broad overlap in substrate inhibitor affinity, absence rodent-human orthologs preclude clinical translation single-gene knockout/knockin findings. At present, changes pharmacokinetics tissue distribution pravastatin, atorvastatin, simvastatin, carboxydichlorofluorescein were studied...
Quantification methods employing stable isotope-labeled peptide standards and liquid chromatography-tandem mass spectrometry are increasingly being used to measure enzyme amounts in biologic samples. Isoform concentrations, combined with catalytic information, can be absorption, distribution, metabolism, excretion studies improve accuracy of vitro/in vivo predictions. We quantified isoforms uridine-diphosphate glucuronosyltransferase (UGT) 1A 2B 12 commercially available recombinant UGTs...
Nanoparticle conjugates have the potential for delivering siRNA, splice-shifting oligomers or nucleic acid vaccines, and can be applicable to anticancer therapeutics. This article compares tripartite with gold nanoparticles synthetic methoxypoly(ethylene glycol)-block-polyamidoamine dendrimers.Interactions model liposomes of a 1:1 molar ratio tripalmitin:cholesterol phospholipid:cholesterol were investigated by high-throughput absorbance, as well fluorescence difference cellular luminescence...
To determine the scaling factors required for inclusion of renal drug glucuronidation clearance in prediction total via (CLUGT ).
Phase II metabolism is prominently governed by UDP-glucuronosyltransferases (UGTs) in humans. These enzymes regulate the bioactivity of many drugs and endogenous small molecules organs, including liver, a major site regulation glucuronidation pathway. This study determined expression hepatic UGTs targeted proteomics 48 liver samples measuring activity using probe substrates. It demonstrates sensitivity accuracy nano-ultra-performance liquid chromatography with tandem mass spectrometry to...
Quantitative characterization of UDP-glucuronosyltransferase (UGT) enzymes is valuable in glucuronidation reaction phenotyping, predicting metabolic clearance and drug-drug interactions using extrapolation exercises based on pharmacokinetic modeling. Different quantitative proteomic workflows have been employed to quantify UGT various systems, with reports indicating large variability expression, which cannot be explained by interindividual alone. To evaluate the effect methodological...
The luminal surface of the small intestine is composed a monolayer cells overlying lamina propria comprised extracellular matrix (ECM) proteins. ECM provides porous substrate critical for nutrient exchange and cellular adhesion. enterocytes within epithelial possess proteins such as transporters, carriers, pumps channels that participate in movement drugs, metabolites, ions amino acids whose function can be regulated or altered by properties ECM. Here, we characterized expression involved...
Curcumin inhibits UDP-glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety concurrent curcumin and administration. Ten participants with advanced solid tumors received one four doses (1, 2, 3, 4 g) phosphatidylcholine complex (PC) orally daily, 200 mg/m
Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic non-immunogenic nanocarriers for drug delivery to unreachable organs tissues, particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs treat Parkinson disease (PD). Specifically, evaluated therapeutic...
Tucatinib is a small molecule tyrosine kinase inhibitor indicated for HER2-positive breast cancer. This recently approved drug primarily metabolized by cytochrome P450 (P450) 2C8 and CYP3A. Given the interindividual variability in pharmacokinetics of some inhibitors, present study explored how CYP2C8 CYP3A activities concentrations can influence overall tucatinib metabolic clearance vitro. depletion, activities, were measured human liver microsomes from 21 donors (males n = 11, females 10)....
Zearalenone (ZEN) is an estrogenic mycotoxin ('mycoestrogen') that contaminates global grain crops leading to detectable concentrations of ZEN and its metabolites, including the synthetic version alpha-zearalanol (ZER), in human populations. Despite vitro vivo animal evidence endocrine disruption by ZEN, there has been limited investigation humans.
Methylenedioxymethamphetamine (MDMA, 'ecstasy'), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by MDMA or one its metabolites has been investigated in vitro. Release both oxytocin and isolated hypothalami obtained male Wistar rats was determined under basal conditions following potassium (40 mM) stimulation. results were compared with those for stimulated release the presence dose range 1 microM to 100 pM...
The global control of tuberculosis (TB) is at risk by the spread multidrug-resistant TB (MDR TB). Treatment MDR lengthy and involves injected drugs, such as capreomycin, that have severe side effects. It was previously reported a single daily dose inhaled capreomycin had positive effect on bacterial burden TB-infected guinea pigs. modest observed possibly due to resulted in insufficient time exposure therapeutic systemic local levels drug. In order determine length drug concentrations are...
Organic cation transporter 1 (OCT1) plays a role in hepatic uptake of drugs, affecting vivo exposure, distinguished primarily through pharmacogenetics the <i>SLC22A1</i> gene. The OCT1 has not been confirmed, however, via drug–drug interactions that similarly affect exposure. In current research, we used Oct1/2 knockout mice to assess Oct1 clearance and liver partitioning clinical substrates model for predicting an effect function on pharmacokinetics humans. Four (sumatriptan, fenoterol,...
UGT enzymes catalyze the formation of glucuronic acid conjugates. Specifically selected representative stable isotope (C(13), N(15)) labeled peptide internal standards each enzyme were employed to quantify UGTs 1A1 and 1A6 by LC-MS/MS using dilution techniques. Inter day variability (n=5) for human liver microsomes was <or= 8.0 % UGT1A1 19 UGT1A6. Comparison within a microsomal library showed strong correlation with Western blot concentrations (r=0.988). The data presented indicates that an...