Thymoquinone-entrapped chitosan-modified nanoparticles: formulation optimization to preclinical bioavailability assessments

Drug Delivery

Sultan Alshehri¹  Syed Sarim Imam¹  Iqra Rahat²  Md. Rizwanullah³  Mohammad Asif⁴  Chandra Kala⁵  Mohamad Taleuzzaman⁵ 

[1] Department of Pharmaceutics, College of Pharmacy, King Saud University;Department of Pharmaceutics, Glocal school of Pharmacy, Glocal University;Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard;Department of Pharmacognosy, Faculty of Pharmacy, Lachoo Memorial College of Science and Technology;Faculty of Pharmacy, Maulana Azad University;

关键词: thymoquinone;    nanoparticles;    chitosan;    polycaprolactone;    pharmacokinetic;   

DOI  :  10.1080/10717544.2021.1927245

来源: DOAJ

【 摘 要 】

The major limitation with the oral administration of most of the phytochemicals is their low aqueous solubility and bioavailability. Thymoquinone (THQ) is one of the most widely used phytochemicals used to treat a variety of diseases. However, strong lipophilic characteristics limit its clinical application. Therefore, this study was aimed to design novel chitosan (C) modified polycaprolactone (PL) nanoparticles (NPs) for improved oral bioavailability of THQ. THQ-CPLNPs was optimized 33-Box–Behnken design. After that, the optimized THQ-CPLNPs was characterized by different parameters. THQ-CPLNPs showed the size, PDI, and ZP of 182.32 ± 6.46 nm, 0.179 ± 0.012, and +21.36 ± 1.22 mV, respectively. The entrapment and loading capacity were found to be 79.86 ± 4.36%, and 13.45 ± 1.38%, respectively. THQ-CPLNPs exhibited burst release in initial 2 h followed by prolonged release up to 24 h in simulated intestinal fluids. THQ-CPLNPs showed excellent mucoadhesion properties which were further confirmed with the intestinal permeation study as well as confocal microscopy. The study revealed higher permeation of THQ-CPLNPs compared to neat THQ suspension (THQ-S). Moreover, in vivo gastric irritation study revealed good compatibility of THQ-CPLNPs with the gastric mucosa. Furthermore, pharmacokinetic results depicted ∼3.53-fold improved oral bioavailability of THQ from THQ-CPLNPs than THQ-S. Therefore, from the findings, it was concluded that the prepared polymeric NPs could be an effective delivery system for improved oral bioavailability of THQ.

【 授权许可】

Unknown