Facile synthesis of mesoporous zinc oxide nanoparticle as a drug delivery system evaluated by IVIVE in PBPK modeling

Abstract This study focuses on the development of mesoporous zinc oxide nanoparticles (mZNPs) via the sol–gel technique, utilizing polyethylene glycol-6000 (PEG-6000) as a capping agent. The research aims to investigate the suitability of these nanoparticles for drug delivery purposes. The analysis of the synthesized material validates the existence of a hexagonal system of zinc oxide with space group P6 3 cm and HRTM confirmed the crystallinity and morphology of the nanoparticles ranging from 15–20 nm, revealing the formation of pores attributed to the presence of PEG-6000. The mZNPs exhibit a BET surface area of 28.3 m 2 . g −1 , with Langmuir surface area measurements indicating 46 m 2 . g −1 . Analysis employing the BJH method outlines pore diameters ranging from approximately 2–5 nm at a relative pressure of around 0.99. Furthermore, these mZNPs demonstrated drug delivery attributes, with 43.3% loading efficiency and 80.33% entrapment efficiency for aspirin. Notably, the release kinetics of aspirin from the mZNPs were investigated in simulated fluids of varying pH, with the highest release (98.1%) observed in simulated intestinal fluid (pH 6.8). The formulation exhibits typical time-dependent release kinetics under mild pH conditions (7.4 and 6.8), while transitioning to erosion-controlled diffusion mechanisms in acidic pH conditions (1.2). Furthermore, mathematical models, including Higuchi’s, Korsmeyer’s, and Weibull’s, were employed to assess release kinetics, offering parameters for in-vitro to in-vivo pharmacokinetic predictions. In the framework of PBPK modeling, renal clearance was computationally simulated at a rate of 45 min −1 , whereas biliary clearance was modeled to occur at 0.05 min −1 . Utilizing these model-derived parameters, the projected half-life of aspirin administered via mZNPs was determined to be 3.1 h. The potential applications of these findings extend to the development of effective drug delivery systems, warranting consideration for future animal model studies involving aspirin and mZNPs.