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

Abstract

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.

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

“…Furthermore, the zeta potential of PNCs suspensions (F1, F2, and F3) was −31 ± 3.10, −35.03 ± 4.80, and −40 ± 5.21, respectively. PCL is known for yielding spherical nanocapsules with negative charge on the surface (Rahat et al., 2021 ). They displayed negative charges owing to PCL structure and its hydrophobic nature which may cause ionization of the carboxylic groups resulting in a negative potential to the interface (Michels et al., 2019 ; Lino et al., 2020 ).…”

“…Therefore, increased concentration of PCL influences negativity of zeta potential of prepared nanocapsules. The high negative zeta potential owing to the charges repulsion toward the natural tendency of aggregation affords stability to nanocapsules from the hostile pH of the biological system (Alves et al., 2016 ; Rahat et al., 2021 ).…”

“…Generally, the high %EE of MN may be attributed to its high lipophilic nature (log P 5.96). Increasing PCL concentration with respect to MN had a considerable effect on %EE, by increasing its concentration the %EE increased (Rahat et al., 2021 ). The relatively high EE value was owing to the high chemotactic between MN and PCL as both are highly hydrophobic; hence, both entities have great affinity toward each other (Govender et al., 2015 ).…”

“…The most commonly used polymers for forming the shell are biocompatible and biodegradable such as poly lactic acid, polylactide-co-glycolide, and poly (Ɛ-caprolactone). Polycaprolactone (PCL) is widely used to prepare different types of nanocapsules comparing to other biodegradable polymers owing to its talented characters; safety, elasticity, cytocompatibility, and very slow biodegradation which were approved by US-FDA (El-Hesaisy & Swidan, 2020 ; Rahat et al., 2021 ). It is also useful to capture a wide range of drugs such as anti-cancer drugs, anti-inflammatories, and immune modulators presenting diverse flexibility with potential applications in therapy (Mahareek et al., 2019 ).…”

Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives

“…Furthermore, the THQ-CS-SLNs showed 3.53 times higher oral bioavailability after single-dose oral administration compared to free THQ. Similarly, the same researchers developed THQ-loaded CS-modified polycaprolactone NPs (THQ-CS-PCL-NPs) and evaluated them for intestinal permeation as well as oral bioavailability in Wistar rats [149]. THQ-CS-PCL-NPs showed excellent mucoadhesive properties and 5.34 times higher intestinal permeation compared to the free drug suspension.…”