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Solid dispersion of mebendazole via surfactant carrier to improve oral bioavailability and in vitro anticancer efficacy

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Abstract

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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Funding

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (NRF-2021R1A2C1011176).

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  1. Thu Nhan Nguyen and Phuong Tran have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, 99 Daehak-Ro, Yuseong-Gu, Daejeon, 34134, Republic of Korea

    Thu Nhan Nguyen, Phuong Tran, Yeong-Eun Choi & Jeong-Sook Park

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  1. Thu Nhan Nguyen
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  2. Phuong Tran
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Correspondence to Jeong-Sook Park.

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All authors (T.N. Nguyen, P. Tran, Y.E. Choi, and J.S. Park) declare that there are no conflicts of interest.

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Nguyen, T.N., Tran, P., Choi, YE. et al. Solid dispersion of mebendazole via surfactant carrier to improve oral bioavailability and in vitro anticancer efficacy. J. Pharm. Investig. 53, 443–455 (2023). https://doi.org/10.1007/s40005-023-00616-z

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  • DOI: https://doi.org/10.1007/s40005-023-00616-z

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