Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies

Int J Nanomedicine. 2018 Dec 18:14:33-43. doi: 10.2147/IJN.S187470. eCollection 2019.

Abstract

Background: Vinpocetine (VNP), a semisynthetic natural product, is used as a vasodilator for cerebrovascular and age-related memory disorders. VNP suffers from low oral bioavailability owing to its low water solubility and extensive first-pass metabolism. This work aimed at utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and alpha lipoic acid (ALA) to develop efficient micellar system for transdermal delivery of VNP.

Materials and methods: VNP-TPGS-ALA micelles were prepared, characterized for particle size using particle size analyzer, and investigated for structure using transmission electron microscope. Optimization of VNP-TPGS-ALA micelles-loaded transdermal films was performed using Box-Behnken experimental design. The investigated factors were percentage of ALA in TPGS (X1), citral concentration (X2), and propylene glycol concentration (X3). Elongation percent (Y1), initial permeation after 2 hours (Y2), and cumulative permeation after 24 hours (Y3) were studied as responses.

Results: Statistical analysis revealed optimum levels of 16.62%, 3%, and 2.18% for X1, X2, and X3, respectively. Fluorescent laser microscopic visualization of skin penetration of the optimized transdermal film revealed marked widespread fluorescence intensity in skin tissue after 0.5, 2, and 4 hours compared with raw VNP transdermal film formulation, which indicated enhancement of VNP skin penetration.

Conclusion: The obtained results highlighted the potentiality of VNP nanostructure-based films for controlling the transdermal permeation of the drug and improving its effectiveness.

Keywords: bioavailability; box behnken design; citral; fluorescent laser microscope; nano-structured-based films; permeation.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Biological Availability
  • Drug Delivery Systems*
  • Fluorescence
  • Humans
  • Micelles*
  • Particle Size
  • Rats
  • Skin / drug effects
  • Skin / metabolism
  • Skin Absorption / drug effects
  • Solubility
  • Thioctic Acid / chemistry*
  • Vinca Alkaloids / administration & dosage*
  • Vinca Alkaloids / pharmacology*
  • Vitamin E / chemistry*

Substances

  • Micelles
  • Vinca Alkaloids
  • Vitamin E
  • vinpocetine
  • Thioctic Acid
  • tocophersolan