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KMID : 1146920230530030443
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Journal of Pharmaceutical Investigation
2023 Volume.53 No. 3 p.443 ~ p.455
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Solid dispersion of mebendazole via surfactant carrier to improve oral bioavailability and in vitro anticancer efficacy
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Thu Nhan Nguyen
Phuong Tran
Choi Yeong-Eun
Park Jeong-Sook
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Abstract
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Purpose : This study aimed to prepare a solid dispersion (SD) formulation of MBZ to improve dissolution and oral bioavailability.
Methods : A SD formulation of mebendazole (MBZ) was prepared using sodium dodecyl sulfate (SDS) as a carrier via lyophilization method. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used to confirm the structural properties and morphology of the MBZ-SD formulation. Dissolution study was conducted in an acidic medium (0.1 M HCl), and pharmacokinetic study was conducted in rats. In addition, the in vitro anticancer effects of MBZ-SD were also investigated in various cancer cell lines.
Results : From the results of PXRD, DSC, FTIR, and SEM assessments, there was an interaction between MBZ and SDS in the MBZ-SD. MBZ-SD significantly improved the aqueous solubility of MBZ (approximately 15,982-fold) and the dissolution of MBZ at 5 min (1.5-fold) as compared to that of pure MBZ. The area under the curve (AUC0?24) and the maximum concentration (Cmax) of the MBZ-SD formulation showed a 3.56- and 3.30-fold increased values compared to pure MBZ. The anticancer effects of MBZ with IC50 value were in the order of A549?>?MDA-MB-231?>?HepG2?>?MCF-7?>?NCI-H1299?>?HeLa. At safe concentrations in normal cells, the MBZ-SD formulation exhibited the superior anticancer efficacy in HeLa cells.
Conclusion : The obtained results in the present study suggests that SD is a good candidate for improving the bioavailability and anticancer effects of MBZ.
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KEYWORD
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Mebendazole, Solid dispersion, Dissolution, Oral bioavailability, Anticancer effect
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