Enhanced extracellular vesicles mediated uttroside B (Utt-B) delivery to Hepatocellular carcinoma cell: Pharmacokinetics based on PBPK modelling.

Autor: Kalishwaralal K; Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 95014, Kerala, India. Electronic address: kalimuthu@rgcb.res.in., Azeez Nazeer A; Laboratory of Pharmaceutical Sciences, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon state, 24341, Republic of Korea., Induja DK; Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, Kerala, India., Keerthana CK; Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 95014, Kerala, India., Shifana SC; Molecular Bioassay Laboratory, Institute of Advanced Virology, Thiruvananthapuram, 695317, Kerala, India., Anto RJ; Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 95014, Kerala, India; Molecular Bioassay Laboratory, Institute of Advanced Virology, Thiruvananthapuram, 695317, Kerala, India.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Apr 09; Vol. 703, pp. 149648. Date of Electronic Publication: 2024 Feb 11.
DOI: 10.1016/j.bbrc.2024.149648
Abstrakt: Our prior investigation has confirmed that the anti-hepatocellular carcinoma activity of the plant saponin, specifically Uttroside B (Utt-B), derived from the leaves of Solanum nigrum Linn. This study concentrated on formulating a novel biocompatible nanocarrier utilizing Extracellular vesicles (EVs) to enhance the delivery of plant saponin into cells. The physicochemical attributes of Extracellular Vesicles/UttrosideB (EVs/Utt-B) were comprehensively characterized through techniques such as Transmission Electron Microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). Despite the promising therapeutic potential of this uttroside B, mechanistic know-how about its entry into cells is still in its infancy. Our research sheds light on the extracellular vesicle-mediated mechanism facilitating the entry of the saponin into cells, a phenomenon confirmed through the use of by confocal microscopy. We further analysed drug-releasing kinetics and simulated the Pharmacokinetics by PBPK modelling. The simulated pharmacokinetics revealed the bioavailability of Uttroside-B in oral administration against intravenous administration.
Competing Interests: Declaration of competing interest There are no conflicts of interest to declare.
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Databáze: MEDLINE