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

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

Osama Aa Ahmed  1   2 , Khalid M El-Say  1   3 , Bader M Aljaeid  1 , Shaimaa M Badr-Eldin  1   4 , Tarek A Ahmed  1   3
Affiliations

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

Osama Aa Ahmed et al. Int J Nanomedicine. .

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.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Particle size distribution measured by particle size analyzer (A) and TEM photomicrographs of VNP-TPGS-ALA micelles (B). Abbreviations: ALA, alpha lipoic acid; TEM, transmission electron microscopy; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate; VNP, vinpocetine.
Figure 2
Figure 2
Ex vivo permeation profile of VNP-TPGS-ALA transdermal patch formulations: F1–F5 (A); F6–F10 (B); and F11–F15 (C). Abbreviations: ALA, alpha lipoic acid; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate; VNP, vinpocetine.
Figure 3
Figure 3
Standard Pareto charts revealing the significance of the independent variables (X1, X2, and X3) and their combined effects on the investigated dependent variables Y1 (A), Y2 (B), and Y3 (C). Notes: X1: ALA in TPGS; X2: citral concentration; X3: PG concentration; Y1: elongation percent; Y2: initial permeation after 2 hours; and Y3: cumulative permeation after 24 hours. Abbreviations: ALA, alpha lipoic acid; PG, propylene glycol; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate.
Figure 4
Figure 4
Three-dimensional response surface plots showing the effects of the independent variables X1 and X2 at midpoint of X3 on the investigated dependent variables Y1 (A and B), Y2 (C), and Y3 (D–F). Notes: X1: ALA in TPGS; X2: citral concentration; X3: PG concentration; Y1: elongation percent; Y2: initial permeation after 2 hours; and Y3: cumulative permeation after 24 hours. Abbreviations: ALA, alpha lipoic acid; PG, propylene glycol; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate; VNP, vinpocetine.
Figure 5
Figure 5
Visualization of skin penetration of the optimized TPGS-ALA-loaded transdermal (left column) and control (right column) films after 0.5, 2, and 4 hours using fluorescence laser microscope (magnification 400×). Abbreviations: ALA, alpha lipoic acid; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate.
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