Nanosized nasal emulgel of resveratrol: preparation, optimization, in vitro evaluation and in vivo pharmacokinetic study

Drug Dev Ind Pharm. 2019 Oct;45(10):1624-1634. doi: 10.1080/03639045.2019.1648500. Epub 2019 Aug 9.

Abstract

Nano-emulgel has become one of the most significant controlled release systems, which has the advantages of both gels and nano-emulsions. This work aims at the formulation of nasal nano-emulgel for resveratrol, employing carbopol 934 and poloxamer 407 as the gelling agents. The optimum nano-emulsion was determined through further characterization of the selected system. The nasal nano-emulgel was prepared and tested for the in vitro release, the release kinetics, FTIR, ex vivo permeation, nasal mucosa toxicity, and in vivo pharmacokinetic study. The optimum nano-emulsion consisted of Tween 20, Capryol 90, and Transcutol at a ratio of (54.26: 23.81: 21.93%v/v), and it exhibited transmittance of 100%, resveratrol solubility of 159.9 ± 6.4 mg/mL, globule size of 30.65 nm. The in vitro resveratrol released from nano-emulsion and nasal nano-emulgel was 96.17 ± 4.43% and 78.53 ± 4.7%, respectively. Ex vivo permeation was sustained during 12 h up to 63.95 ± 4.7%. The histopathological study demonstrated that the formula is safe and tolerable to the nasal mucosa. Cmax and AUC (0-∞) of resveratrol obtained after nasal administration of nasal nano-emulgel was 2.23 and 8.05 times, respectively. Similarly, Tmax was increased up to 3.67 ± 0.82 h. The optimized nasal nano-emulgel established intranasal safety and bioavailability enhancement so it is considered as a well-designed system to target the brain.

Keywords: Nano-emulgel; brain targeting; emulsion; pharmacokinetics; resveratrol.

MeSH terms

  • Administration, Intranasal / methods
  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Drug Delivery Systems / methods
  • Emulsions / chemistry*
  • Emulsions / pharmacokinetics*
  • Gels / chemistry*
  • Gels / pharmacokinetics*
  • Male
  • Nasal Mucosa / metabolism*
  • Poloxamer / chemistry
  • Polymers / chemistry
  • Polysorbates / chemistry
  • Propylene Glycols / chemistry
  • Rats
  • Rats, Wistar
  • Resveratrol / chemistry*
  • Resveratrol / pharmacokinetics*
  • Solubility / drug effects

Substances

  • Emulsions
  • Gels
  • Polymers
  • Polysorbates
  • Propylene Glycols
  • capryol propylene glycol monocaprylate
  • Poloxamer
  • Resveratrol