Abstract
Introduction: Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident. It affects angiogenesis, apoptosis, and invasion, and plays a key role in the production of carcinogens. It has also been reported that COX-2 inhibitors such as celecoxib (CLX) might play an effective role in preventing cancer formation and progression. Formulation of CLX into nanovesicles is a promising technique to improve its bioavailability and anticancer efficacy. Aim: The aim of this study is to optimize and evaluate the anticancer efficacy of CLX-loaded in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles in-vitro and determine its pharmacokinetic parameters in-vivo. Methods: The novel provesicular powders were prepared by the slurry method and optimized by 32 full factorial design using the desirability function. Results: Small mean particle size was achieved by the formed vesicles with value of 351.7 ± 1.76 nm and high entrapment efficacy of CLX in the formed vesicles of 97.53 ± 0.84%. Solid state characterization of the optimized formulation showed that the powder was free flowing, showed no incompatibilities between drug and excipients and showed smooth texture. The cytotoxic study of the optimized formula on HCT-116, HepG-2, A-549, PC-3 and MCF-7 cell lines showed significant increase in activity of CLX compared to its free form. The pharmacokinetic study on albino rabbits after oral administration showed significant increase in the area under the curve (AUC)0–24 h and significantly higher oral relative bioavailability of the optimized formulation compared to Celebrex® 100 mg market product (p < 0.05). Conclusion: All findings of this study suggest the potential improvement of efficacy and bioavailability of CLX when formulated in the form of in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles for its repositioned use as an anticancer agent.
Highlights
Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident
The lowest Particle size (PS) records were observed in formulations with the highest amount of span 40; formulation F9 (600 mg span 40, 351.7 ± 1.76 nm) and the largest PS values were remarked in formulations with the lowest amount of span 40; formulation F1 (200 mg span 40, 621.2 ± 2.82 nm)
Low insufficient quantity of surface active agent in lipid-based nanocarriers causes instability [33]. This observation agrees with findings observed by Negi et al who studied the impact of surfactant concentration on the vesicle size of venlafaxine niosomes [34]
Summary
Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident. Aim: The aim of this study is to optimize and evaluate the anticancer efficacy of CLX-loaded in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles in-vitro and determine its pharmacokinetic parameters in-vivo. Conclusion: All findings of this study suggest the potential improvement of efficacy and bioavailability of CLX when formulated in the form of in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles for its repositioned use as an anticancer agent. Among the promising new vesicular systems are in-situ forming provesicular drug carriers, which are pro-nanovesicles consisting of dry free flowing powder coated with surfactant, which can be hydrated just before use resulting in the formation of the nanovesicles facilitating the absorption of the incorporated drugs [11,12]. It is assumed that encapsulation of CLX into novel fatty alcohol, non-ionic surfactant-based, in-situ forming provesicular powder could improve its anticancer activity as well as its bioavailability. A pharmacokinetic study was conducted to evaluate the bioavailability of CLX-IPP optimized formula in comparison to CLX market capsules
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