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

Expert Opin Drug Deliv. 2024 May;21(5):779-796. doi: 10.1080/17425247.2024.2361117. Epub 2024 May 31.

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.

Keywords: Fatty liver; controlled release; hyperlipidemia; lovastatin; nanoemulsomes.

MeSH terms

  • Animals
  • Bile Acids and Salts* / chemistry
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Stability*
  • Emulsions*
  • Fatty Acids* / administration & dosage
  • Fatty Acids* / chemistry
  • Lovastatin* / administration & dosage
  • Lovastatin* / chemistry
  • Lovastatin* / pharmacokinetics
  • Male
  • Nanoparticles / chemistry
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Particle Size*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bile Acids and Salts
  • Lovastatin
  • Fatty Acids
  • Emulsions
  • Drug Carriers