Isolation, Formulation, and Efficacy Enhancement of Morin Emulsified Carriers Against Lung Toxicity in Rats

AAPS PharmSciTech. 2018 Jul;19(5):2346-2357. doi: 10.1208/s12249-018-1072-6. Epub 2018 Jun 4.

Abstract

The present study demonstrates a preparative medium-pressure liquid chromatography (MPLC) method for isolation of Morin besides evaluating its efficacy in comparison with its self-nanoemulsifying drug delivery (SNEDD) and nanoemulsion (NE) systems against in-vivo HgCl2-induced lung toxicity in rats. Morin was isolated from hydroalcoholic (70%) extract of Psidium guajava leaves by MPLC. The purity (> 90%) was done using HPLC. Screening of Morin solubility was studied to identify the components of each system. The prepared formulae were assessed for their thermodynamic stability, rheological properties, emulsification time, size, zeta potential beside its dissolution. The selected formulae according to the smallest size, highest zeta potential, and release at Q10 min were assessed for their morphology by transmission electron microscopy (TEM) and protective potential against in-vivo HgCl2-induced lung toxicity in rats. All formulae were stable with Newtonian flow, emulsification time was (< 134 ± 10 s), size (< 40 nm) with zeta potential (> - 10.36 ± 0.99 mV). The extent of free Morin dissolved from capsule showed significantly the lowest percent released (22.21 ± 1.45%) while in case of SNEDDs and NEs (> 55% dissolved). The morphology of the selected Morin formulae showed spherical shape within the nano-range. Supplementation of Morin and its formulae to rats caused significant decrease in C-reactive protein, hepatoglobin, hydroproxide, lung nitric oxide, tumor necrosis factor-α, immunoglobulin (E and G), histamine, malondialdehyde, and interleukin-6 gene expression while significant increase in immunoglobulin A, caspase-3, catalase, and glutathione peroxidase compared to HgCl2. SNEDD and NE formulae could ameliorate lung toxicity in a mechanism related to their antioxidant and anti-inflammatory potential.

Keywords: MPLC; Morin; drug delivery system; emulsified carriers; lung toxicity.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry*
  • Antioxidants / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Compounding
  • Drug Delivery Systems / methods
  • Emulsions / administration & dosage
  • Emulsions / chemistry*
  • Emulsions / metabolism
  • Flavonoids / administration & dosage
  • Flavonoids / chemistry*
  • Flavonoids / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Mercuric Chloride / toxicity*
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry
  • Particle Size
  • Rats
  • Rats, Wistar
  • Solubility

Substances

  • Antioxidants
  • Drug Carriers
  • Emulsions
  • Flavonoids
  • Mercuric Chloride
  • morin