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Systematic Optimization of Solid Lipid Nanoparticles of Silybin for Improved Oral Drug Delivery by Box-Behnken Design: In Vitro and In Vivo Evaluations

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Abstract

Purpose

Silybin (SB) is the most potent flavonolignan extracted from the milk thistle plant, showing anti-oxidative properties. Owing to the lipophilic nature of SB, the oral bioavailability of SB is low. This study developed and optimized SB loaded solid lipid nanoparticles (SB-SLNs), and evaluated their in vitro and in vivo characteristics.

Methods

The applied method of SLNs production was solvent emulsification and evaporation, using stearic acid as the solid lipid core and Cremophor® RH40 as the surfactant. The statistical optimization was determined using Box-Behnken design. The morphology of the optimized silybin-loaded SLNs was detected by scanning electron microscopy. Also, differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FTIR), and powder X-ray diffractometry (P-XRD) were used to characterize SLNs’ physicochemical properties. Moreover, in vivo studies for pharmacokinetic properties of SB were performed on male Wistar rats.

Results

The optimum formulation exhibited the size of 262.36 ± 12 nm, and -22.22 ± 0.87 mV of zeta potential and 74.02 ± 1.66% of entrapment efficiency. The scanning electron microscopy(SEM) images demonstrated the rough-surfaced ovate structure of SB-SLNs, and solid-state research evince the amorphous state of SB-SLNs. The in vivo evaluations showed an increased bioavailability of SLN formulation higher than pure SB in plasma.

Conclusion

The significant improvement of SB-SLNs pharmacokinetic properties after single oral dose administration specified SLNs as a capable drug delivery system for SB.

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Acknowledgements

The authors are grateful to all colleagues and staff members in the Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences.

Funding

This work was supported financially (Grant No. 980120168) by the Hamadan University of Medical Sciences, Hamadan, Iran. 

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Medicinal Plants & Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Zeynab Nazem, Farzin Firoozian, Saeideh Khodabandelou & Mohammad Mehdi Mahboobian

  2. Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants & Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Mojdeh Mohammadi

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  1. Zeynab Nazem
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  2. Farzin Firoozian
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Correspondence to Mohammad Mehdi Mahboobian.

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Nazem, Z., Firoozian, F., Khodabandelou, S. et al. Systematic Optimization of Solid Lipid Nanoparticles of Silybin for Improved Oral Drug Delivery by Box-Behnken Design: In Vitro and In Vivo Evaluations. J Pharm Innov 18, 472–484 (2023). https://doi.org/10.1007/s12247-022-09637-x

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