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

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Materials Science

Background:

• Phytochemicals like thymoquinone (THQ) have therapeutic potential but suffer from poor oral bioavailability due to low aqueous solubility and lipophilicity.
• Effective delivery systems are crucial to overcome these limitations for enhanced clinical application of THQ.

Purpose of the Study:

• To design and characterize novel chitosan (C) modified polycaprolactone (PL) nanoparticles (NPs) for improved oral delivery of thymoquinone (THQ).
• To evaluate the physicochemical properties, drug release, mucoadhesion, permeation, gastric compatibility, and pharmacokinetic profile of the developed THQ-loaded nanoparticles.

Main Methods:

• Chitosan-modified polycaprolactone nanoparticles (THQ-CPLNPs) were synthesized and optimized using a 33-Box-Behnken design.
• Characterization included size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity.
• In vitro drug release, mucoadhesion, intestinal permeation, and in vivo gastric irritation studies were performed.
• Pharmacokinetic analysis was conducted to determine the oral bioavailability enhancement.

Main Results:

• Optimized THQ-CPLNPs exhibited a particle size of 182.32 ± 6.46 nm, PDI of 0.179 ± 0.012, and ZP of +21.36 ± 1.22 mV.
• Entrapment and loading capacities were 79.86 ± 4.36% and 13.45 ± 1.38%, respectively.
• THQ-CPLNPs demonstrated sustained release over 24 hours, excellent mucoadhesion, enhanced intestinal permeation compared to neat THQ, and good gastric compatibility.
• Pharmacokinetic studies revealed approximately 3.53-fold higher oral bioavailability of THQ from THQ-CPLNPs compared to THQ suspension.

Conclusions:

• Chitosan-modified polycaprolactone nanoparticles represent a promising and effective delivery system for enhancing the oral bioavailability of thymoquinone.
• The developed nanocarrier system overcomes the limitations of poor solubility and lipophilicity of THQ, paving the way for improved therapeutic outcomes.