Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization, in vitro characterization, cell line studies and in vivo efficacy in schizophrenia

Abstract

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration.

Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies.

Results: The LH-SLNs had PS of 139.8 ± 5.5 nm, EE of 79.10 ± 2.50% and zeta potential of −30.8 ± 3.5 mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia.

Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.

Keywords:

• Lurasidone HCl
• solid lipid nanoparticles
• Caco-2 cells
• intestinal lymphatic uptake
• bioavailability enhancement
• in vivo studies

Acknowledgments

The authors thank Alembic Pharmaceuticals Ltd., Vadodara, India, for providing Lurasidone HCl as a gift sample. Authors are also grateful to Dr. Vikram Sarabhai Institute of Cell and Molecular Biology, The M. S. University of Baroda for providing flow cytometry and confocal facility.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are grateful to Department of Science and Technology (DST), New Delhi, India, for providing “Innovation in Science Pursuit for Inspired Research (INSPIRE)” Fellowship and contingency to Mitali Patel.