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 (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

Acknowledgments

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no G-99-166-38. The authors, therefore, acknowledge with thanks, the DSR for technical and financial support.

Disclosure

The authors report no conflicts of interest in this work.