Enhanced Oral Bioavailability of Epalrestat SBE7-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation

Zunaira Alvi; Muhammad Akhtar; Arshad Mahmood; Nisar Ur-Rahman; Imran Nazir; Hadia Sadaquat; Muhammad Ijaz; Shahzada Khurram Syed; Muhammad Khurram Waqas; Yi Wang

doi:10.2147/IJN.S339857

Enhanced Oral Bioavailability of Epalrestat SBE₇-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation

Int J Nanomedicine. 2021 Dec 29:16:8353-8373. doi: 10.2147/IJN.S339857. eCollection 2021.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab, 63100, Pakistan.
² Department of Medical Laboratory Technology, Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur, Bahawalpur, Punjab, 63100, Pakistan.
³ College of Pharmacy, Al Ain University, Abu Dhabi Campus, Abu Dhabi, United Arab Emirates.
⁴ Department of Pharmacy, Royal College of Medical Sciences (RIMS), Multan, Punjab, 60000, Pakistan.
⁵ Bahawal Victoria Hospital, Bahawalpur, Punjab, 63100, Pakistan.
⁶ Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.
⁷ Department of Basic Medical Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan.
⁸ Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan.
⁹ Center for Advanced Low-Dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201600, People's Republic of China.

Abstract

Background: Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined.

Purpose: Current research aimed to fabricate inclusion complexation of EPL with SBE₇ β-CD (IC) and EPL/SBE₇ β-CD CS NPs (NP).

Methods: EPL was complexed with SBE₇ β-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug's antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP.

Results: The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE₇ β-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be -6.6 kcal/mol. The calculated C_max values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 μg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC_0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 μg/mL*h, respectively.

Conclusion: Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

Keywords: HPLC; epalrestat; inclusion complexation; nanoparticles; pharmacokinetic evaluation.

MeSH terms

Animals
Biological Availability
Chitosan*
Drug Carriers
Molecular Docking Simulation
Nanoparticles*
Particle Size
Rabbits
Rhodanine / analogs & derivatives
Thiazolidines

Substances

Drug Carriers
Thiazolidines
epalrestat
Rhodanine
Chitosan