Exploiting Apical Sodium-Dependent Bile Acid Transporter (ASBT)-Mediated Endocytosis with Multi-Functional Deoxycholic Acid Grafted Alginate Amide Nanoparticles as an Oral Insulin Delivery System.

Autor: Razmjooei M; Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran., Hosseini SMH; Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran., Yousefi G; Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ghyousefi@sums.ac.ir.; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran. ghyousefi@sums.ac.ir., Golmakani MT; Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran., Eskandari MH; Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran. eskandar@shirazu.ac.ir.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2024 Feb; Vol. 41 (2), pp. 335-353. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1007/s11095-023-03641-7
Abstrakt: Objective: Oral administration of insulin is a potential candidate for managing diabetes. However, it is obstructed by the gastrointestinal tract barriers resulting in negligible oral bioavailability.
Methods: This investigation presents a novel nanocarrier platform designed to address these challenges. In this regard, the process involved amination of sodium alginate by ethylene diamine, followed by its conjugation with deoxycholic acid.
Results: The resulting DCA@Alg@INS nanocarrier revealed a significantly high insulin loading content of 63.6 ± 1.03% and encapsulation efficiency of 87.6 ± 3.84%, with a particle size of 206 nm and zeta potentials of -3 mV. In vitro studies showed sustained and pH-dependent release profiles of insulin from nanoparticles. In vitro cellular studies, confocal laser scanning microscopy and flow cytometry analysis confirmed the successful attachment and internalization of DCA@Alg@INS nanoparticles in Caco-2 cells. Furthermore, the DCA@Alg@INS demonstrated a superior capacity for cellular uptake and permeability coefficient relative to the insulin solution, exhibiting sixfold and 4.94-fold enhancement, respectively. According to the uptake mechanism studies, the results indicated that DCA@Alg@INS was mostly transported through an energy-dependent active pathway since the uptake of DCA@Alg@INS by cells was significantly reduced in the presence of NaN 3 by ~ 92% and at a low temperature of 4°C by ~ 94%.
Conclusions: Given the significance of administering insulin through oral route, deoxycholic acid-modified alginate nanoparticles present a viable option to surmount various obstacles presented by the gastrointestinal.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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