Department of Pharmacy

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Author: search.filters.author.Taliyan, RajeevSubject: search.filters.subject.Pharmacokinetics

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    Pharmacokinetic and Biodistribution Studies of Camel Milk Casein Nanoparticles Loaded Sorafenib in Swiss Albino Mice
    (Springer, 2024-06) Taliyan, Rajeev; Dubey, Uma S.
    Sorafenib, a multikinase inhibitor, is used for the treatment of advanced stages of hepatic and renal carcinoma patients. However, sorafenib’s low solubility, low bioavailability, unfavorable pharmacokinetic properties, and undesirable side effects are barriers that restrict its utility. This study aims to overcome these problems by encapsulating sorafenib in a novel camel milk casein nanoparticles. Calcium chloride–linked casein nanoparticles were prepared, lyophilized, and characterized for size distribution, zeta potential, and polydispersity index by using a zeta sizer. Drug encapsulation efficiency and drug loading efficiency of these nanoparticles were also determined by UV spectroscopy. Further, in vivo pharmacokinetic and biodistribution studies were conducted in healthy Swiss albino mice. Bioanalytical method was developed by HPLC for quantitative evaluation of the drug in mice plasma, liver, lungs, kidney, heart, and spleen. Multiple pharmacokinetic parameters like T1/2, AUC, clearance, etc. were analyzed through Phoenix Winolin software. Our pharmacokinetic study showed that sorafenib encapsulation within casein nanoparticles (SFN-CasNPs) significantly increased its bioavailability, as exhibited by an enhanced Cmax (3.8-fold) and AUC (1.42-fold). Also, the half-life (t1/2)) of the encapsulated drug increased by 2 h as compared to free drug. Furthermore, biodistribution study showed an increased accumulation of SFN-CasNPs in the liver and kidney as compared to all other tissues, whereas the free drug showed its maximum accumulation in the heart indicating cardiotoxicity. This accumulation of sorafenib was significantly reduced when it was encapsulated within the camel milk casein nanoparticle. This study has highlighted the significance of using camel milk casein nanoparticles for drug delivery owing to an enhanced bioavailability of the sorafenib in an encapsulated form. The reduced accumulation of sorafenib in an encapsulated form also indicates a reduced risk of cardiotoxicity. In the future, clinical trials may be performed on hepatocellular caricinoma patients, after enhancing the selectivity of the drug towards the liver.
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    Pharmacokinetics and toxicity considerations for antibody–drug conjugates: an overview
    (Future Science Group, 2023-09) Taliyan, Rajeev
    Antibody–drug conjugates (ADCs) is one of the fastest-growing drug-delivery systems. It involves a monoclonal antibody conjugated with payload via a ligand that directly targets the expressive protein of diseased cell. Hence, it reduces systemic exposure and provides site-specific delivery along with reduced toxicity. Because of this advantage, researchers have gained interest in this novel system. ADCs have displayed great promise in drug delivery and biomedical applications. However, a lack of understanding exists on their mechanisms of biodistribution, metabolism and side effects. To gain a better understanding of the therapeutics, careful consideration of the pharmacokinetics and toxicity needs to be undertaken. In this review, different pharmacokinetics parameters including distribution, bioanalysis and heterogeneity are discussed for developing novel therapeutics.
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    Preclinical pharmacokinetics of trigonelline using ultra-performance liquid chromatography–tandem mass spectrometry and pharmacological studies targeting type 2 diabetes
    (Wiley, 2021-03) Taliyan, Rajeev
    Trigonelline is a quaternary base alkaloid and zwitterionic complex that acts by affecting β-cell regeneration and insulin secretion. Tr inhibits enzymatic activities, lowering the blood glucose and lipid levels due to which it is used in the treatment of co-morbid diseases such as diabetes, Alzheimer's, etc. Herein, it was aimed to develop a bioanalytical method for estimation of Tr using ultra-performance liquid chromatography–tandem mass spectrometry and explore the pharmacokinetic profile. The anti-diabetic, antilipidemic efficacy studies of Tr in the high-fat diet-induced streptozotocin-diabetic rat model was also explored. The separation of analyte was achieved with acetonitrile and 0.1% formic acid (20:80) with a flow of 0.4 mL/min. The ionization of the analyte was achieved in positive electrospray ionization mode with the precursor to product ion transitions of Tr (138.14 > 94), and Trigonelline D3 (143.19 > 97.13). The validated assay was effectively applied for the estimation of compartmental pharmacokinetic by using Phoenix WinNolin8.0 (Certera™, USA) and it was observed that the Tr follow two compartmental pharmacokinetic model. The experimental results also suggest that Tr distributed through the central compartment to the peripheral compartment and redistributed to the central compartment. In addition, Tr exhibited significant anti-hyperglycemic and antihyperlipidemic efficacy against high-fat diet-induced streptozotocin-induced type 2 diabetic rats.
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    Pre-clinical pharmacokinetic and pharmacodynamic modelling study of 4-hydroxyisoleucine using validated ultra-performance liquid chromatography-tandem mass spectrometry
    (RSC, 2020) Taliyan, Rajeev
    A reliable and sensitive ultra-performance liquid chromatography-tandem mass spectrometry-based method has been developed for the estimation of 4-hydroxyisoleucine (4-HI), a potent insulinotropic and hypolipidemic agent. The extraction of 4-HI from plasma was accomplished by the protein precipitation technique using L-isoleucine as an internal standard. The separation of analytes was achieved with a mobile phase consisting of acetonitrile and 0.1% formic acid in an isocratic flow system on a BEH Shield RP-18 column (150 mm × 2.1 mm, 1.7 μm). 4-HI and L-isoleucine were detected using an electrospray ionization (ESI) ion source, using multiple reaction monitoring (MRM) in positive ion mode. The precursor to product ion transitions of 4-HI and L-isoleucine were found at m/z values of 148.19 > 74.02 and 132.17 > 69.04, respectively. As per the guidelines for bioanalytical methods, all validation parameter results were within the acceptable range. The method exhibited a robust and reproducible linearity range of 1–5000 ng mL−1 with a coefficient of regression of 0.9999. The method was successfully applied for the estimation of pharmacokinetic parameters after oral administration of 4-HI (10 mg kg−1) in Wistar rats, by using Thoth Pro (version: 4.3) software. Herein, the two-compartment model was statistically fitted based on AIC and SBC values for evaluation of the pharmacokinetic parameters of 4-HI. Pharmacodynamic studies were also performed by measuring the levels of triglyceride and total cholesterol, and showed that the pharmacokinetic and pharmacodynamic data of 4-HI correlated with each other.