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

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 (X ₁), citral concentration (X ₂), and propylene glycol concentration (X ₃). Elongation percent (Y ₁), initial permeation after 2 hours (Y ₂), and cumulative permeation after 24 hours (Y ₃) were studied as responses.

Results

Statistical analysis revealed optimum levels of 16.62%, 3%, and 2.18% for X ₁, X ₂, and X ₃, 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.