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.2015 Sep 18:10:5837-51.
doi: 10.2147/IJN.S86186. eCollection 2015.

Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes

Affiliations

Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes

Andreia Ascenso et al. Int J Nanomedicine..

Abstract

Ultradeformable vesicles (UDV) have recently become a promising tool for the development of improved and innovative dermal and transdermal therapies. The aim of this work was to study three related UDV: transfersomes, ethosomes, and transethosomes for the incorporation of actives of distinct polarities, namely, vitamin E and caffeine, and to evaluate the effect of the carrier on skin permeation and penetration. These actives were incorporated in UDV formulations further characterized for vesicles imaging by transmission electron microscopy; mean vesicle size and polydispersity index by photon correlation spectroscopy; zeta potential by laser-Doppler anemometry; deformability by pressure-driven transport; and incorporation efficiency (IE) after actives quantification by high-performance liquid chromatography. Topical delivery studies were performed in order to compare UDV formulations regarding the release, skin permeation, and penetration profiles. All UDV formulations showed size values within the expected range, except transethosomes prepared by "transfersomal method", for which size was smaller than 100 nm in contrast to that obtained for vesicles prepared by "ethosomal method". Zeta potential was negative and higher for formulations containing sodium cholate. The IE was much higher for vitamin E- than caffeine-loaded UDV as expected. For flux measurements, the following order was obtained: transethosomes (TE) > ethosomes (E) ≥ transfersomes (T). This result was consistent with the release and skin penetration profiles for Vitamin E-loaded UDV. However, the releasing results were totally the opposite for caffeine-loaded UDV, which might be explained by the solubility and thermodynamic activity of this active in each formulation instead of the UDV deformability attending to the higher non-incorporated fraction of caffeine. Anyway, a high skin penetration and permeation for all caffeine-loaded UDV were obtained. Transethosomes were more deformable than ethosomes and transfersomes due to the presence of both ethanol and surfactant in their composition. All these UDV were suitable for a deeper skin penetration, especially transethosomes.

Keywords: caffeine; lipid vesicles; topical delivery studies; vitamin E.

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Figures

Figure 1
Figure 1
Schematic representation of ultradeformable vesicles.Notes: (A) Transfersomes. (B) Ethosomes. (C) Transethosomes. Adapted from: Vinod KR, Kumar MS, Anbazhagan S, et al. Critical issues related to transfersomes – novel vesicular system.Acta Sci Pol Technol Aliment. 2012;11(1):67–82.
Figure 2
Figure 2
Schematic representation of ultradeformable vesicles permeation and penetration through the skin.
Figure 3
Figure 3
Macroscopic appearance of ultradeformable vesicles formulations.Note: Transfersomes, ethosomes, and transethosomes (from left to right).
Figure 4
Figure 4
Microscopic appearance of ultradeformable vesicle formulations obtained by transmission electron microscopy.
Figure 5
Figure 5
Flux of the different formulations after pressure filtration expressed as mean ± standard deviation (g/s).Notes: A and B at the end of the legend refer to the method employed for the vesicles preparation, method A or method B, respectively. For each formulation, the flux was performed in triplicate (n=3). Statistical analysis: One Way Anova with All Pairwise Multiple Comparison Procedures; means with different letters (a,b,c) and different numbers are significantly different (P<0.05). The letters are also numerated according to each group.Abbreviations: E caf, caffeine-loaded ethosomes; empty E, empty ethosomes; empty TE NaCo, empty sodium cholate transethosomes; empty TE span, empty Span 20 transethosomes; empty T Naco, empty sodium cholate transfersomes; empty T span, empty Span 20 transfersomes; E vitE, vitamin E-loaded ethosomes; T caf NaCo, caffeine-loaded sodium cholate transfersomes; T caf span, caffeine-loaded Span 20 transfersomes; TE caf NaCo, caffeine-loaded sodium cholate transethosomes; TE caf span, caffeine-loaded Span 20 transethosomes; TE vitE NaCo, vitamin E-loaded sodium cholate transethosomes; T vitE NaCo, vitamin E-loaded sodium cholate transfersomes.
Figure 6
Figure 6
Cumulative amount of vitamin E ultradeformable vesicle formulation released over 6 hours, expressed as mean (absolute value and %) ± standard deviation.Notes: Data were collected from six samples (n=6 per formulation) at each hour using Franz cells. Statistical analysis: two-way analysis of variance with duplicates and all pairwise multiple comparison procedures; means with different letters (a,b,c) are significantly different (P<0.05).Abbreviations: E vitE, vitamin E-loaded ethosomes; TE vitE NaCo, vitamin E-loaded sodium cholate transethosomes; T vitE NaCo, vitamin E-loaded sodium cholate transfersomes.
Figure 7
Figure 7
(A) Cumulative amount of caffeine UDV formulation (prepared with sodium cholate) released over 6 hours, expressed as mean ± SD. (n=6 per formulation). (B) Cumulative amount of caffeine UDV formulation (prepared with sodium cholate) released over 6 hours relative to the applied amount, expressed as mean ± SD (n=6 per formulation). (C) Cumulative amount of Caffeine solution controls released over 6 hours, expressed as mean ± SD (n=3 per control). (D) Cumulative amount of caffeine solution controls released over 6 hours relative to the applied amount, expressed as mean ± SD (n=3 per control).Notes: Statistical analysis: two-way analysis of variance with duplicates and all pairwise multiple comparison procedures; means with different letters (a,b and c) are significantly different (P<0.05).Abbreviations: E caf, caffeine-loaded ethosomes; Solution Control E, control solution for ethosomes; Solution Control T, control solution for transfersomes; Solution Control TE, control solution for transethosomes; SD, standard deviation; T caf NaCo, caffeine-loaded sodium cholate transfersomes; TE caf NaCo, caffeine-loaded sodium cholate transethosomes; UDV, ultradeformable vesicles.
Figure 8
Figure 8
Retention of vitamin E ultradeformable vesicle formulations in SC and ED after 24 hours, expressed as mean (µg/cm2 or %/cm2) ± standard deviation (n=3 per formulation).Notes: Statistical analysis: one-way analysis of variance with all pairwise multiple comparison procedures (Holm–Sidak method); means with different letters are significantly different (P<0.05).Abbreviations: ED, epidermis plus dermis; E vitE, vitamin E-loaded ethosomes; SC, stratum corneum; TE vitE NaCo, vitamin E-loaded sodium cholate transethosomes; T vitE NaCo, vitamin E-loaded sodium cholate transfersomes.
Figure 9
Figure 9
Retention of caffeine UDV formulations, and the respective solutions controls in SC and ED and skin permeation after 24 hours, expressed as mean (µg/cm2 or %/cm2) ± standard deviation (n=3 per formulation).Notes: Statistical analysis: one-way analysis of variance with all pairwise multiple comparison procedures (Holm–Sidak method) between each group (UDV versus respective controls and transfersomes versus ethosomes versus transethosomes); means with different letters are significantly different (P<0.05).Abbreviations: E caf, caffeine-loaded ethosomes; ED, epidermis plus dermis; SC, stratum corneum; T caf NaCo, caffeine-loaded sodium cholate transfersomes; TE caf NaCo, caffeine-loaded sodium cholate transethosomes; UDV, ultradeformable vesicles.
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