Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, in-vitro, ex-vivo, and in-vivo analyses

ABSTRACT

Background

Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles.

Methods

Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties.

Results

Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency values of 270 ± 27.4 nm, −23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope. In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones.

Conclusion

Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

Graphical Abstract

KEYWORDS:

• Fatty liver
• lovastatin
• nanoemulsomes
• controlled release
• hyperlipidemia

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

SA Faran: Conceptualization, Investigation, Methodology, Experimental Work, Data curation, Writing – original draft. T Hussain: Methodology. SH Khalid: Data curation, Validation. I U Khan: Methodology, Validation, Data curation. M Asif: Conceptualization, Methodology. J Ahmad: Methodology. A Rehman: Methodology. S Asghar: Supervision, Conceptualization, Validation, Funding acquisition, Resources, Data curation, Writing – review and editing.

Acknowledgments

The authors thank Nabiqasim Industries, Pakistan, for providing free sample of Lovastatin. The authors are also grateful to Lipoid AG, Switzerland for providing Phospholipon 90 G.

Ethics approval

The inclusion of animal experiments in this study was performed in line with the principles of the Declaration of Helsinki. All the guidelines were approved by the Institutional Review Board (IRB) based at Government College University Faisalabad, Faisalabad 38,000, Pakistan. (Ref No. GCUF/ERC/2010, Study No. 19610, IRB No. 610, Dated 25 March 2019).

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425247.2024.2361117.

Additional information

Funding

This work was funded under the Higher Education Commission of Pakistan’s project [grant number: 5663/Punjab/NRPU/R&D/HEC/2016].