Phospholipid nanoformulation of thymoquinone with enhanced bioavailability: Development, characterization and anti-inflammatory activity

Abstract

Thymoquinone (TQ), a potent bioactive of Nigella sativa plant, is highly hydrophobic molecule and thus associated with poor oral bioavailability. The present work proposes the phospholipid-nanoparticles (PLN) based delivery of TQ to enhance the low oral bioavailability and anti-inflammatory activity. TQ-loaded nanoparticles were prepared via micro-emulsification technique employing different phospholipid concentrations and extensively characterized for particle size, surface charge, surface morphology, entrapment efficiency, and drug release kinetics. Further, the nanoparticles were assessed for oral bioavailability, and anti-inflammatory activity employing rat paw edema model. The optimized nanoparticle composition (F1) was nanosized (<100 nm) with spherical morphology coupled with narrow size distribution, higher drug entrapment efficiency (>70%), controlled drug release pattern, and negatively charged surface (zeta potential of −0.57 mV). After oral administration of a single dose of F1 formulation, showed approx. 226.6% relative bioavailability vis-à-vis plain TQ suspension. While, substantially higher reduction in the percent inhibition in paw edema in comparison to the pure drug suspension and diclofenac sodium, was observed in the inflammation model. The present work indicate that PLN could be an efficient nanodevices for the treatment of inflammatory disorders and promising carrier system to augment TQ oral bioavailability.