Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation

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.

Engineering 5-flourouracil and leucovorin-loaded vesicular systems for possible colon specific delivery: In vitro evaluation and real time cell assay against HCT-116 colon cell lines

“…This pattern (increased particle size) was also observed when Tween 60 concentration was increased from 50 % (P8) to 70 % (P7). Our results are consistent with those of previous studies [ [23] , [24] , [25] , [26] , 27 ]. Vesicle size is critical for nanovesicular carriers because it influences stability, entrapment efficiency, bioavailability, and bio-distribution.…”

“…In our results it is seen that the particles of the DEX or LAC or NEU were coated with the surfactant and lipid mix. Nasr and his team [ 25 ] reported smoother surfaces with the LAC-based proniosomes when compared to the LAC. They explained that the smooth surfaces observed were due to the packing effects of the surfactants used, and further buttressed that the thickness observed was a result of the deposition of the surfactant – cholesterol mixture at various points of deep invaginations on lactose [ 25 ].…”

Development, Optimization, and In Vitro/In Vivo Evaluation of Azelaic Acid Transethosomal Gel for Antidermatophyte Activity

“…Infrared spectra of the free drug AzA, medicated optimized formula and the plain formula (without drug) were attained using FTIR spectrophotometer VERTEX 70 (Bruker Corporation, Karlsruhe, Germany) [ 26 ]. The spectra were analyzed in the range of 500 to 4000 cm −1 .…”

Investigating the Impact of Optimized Trans-Cinnamic Acid-Loaded PLGA Nanoparticles on Epithelial to Mesenchymal Transition in Breast Cancer

“…In vitro drug release of CIN from CIN-PLGA-NPs optimized formulation was performed utilizing the dialysis bag technique and compared with free CIN. 31 , 32 Cellulose dialysis bag was presoaked in distilled water for 12 h. CIN-PLGA-NPs equivalent to 10 mg of CIN were exactly weighed and the same weight of free CIN was resuspended in phosphate buffer solution (PBS) of pH 7.4 and vortexed for 2 min. After that, they were transferred into the dialysis bags, and both ends of the bags were tightly closed.…”