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. 2023 Aug 3;9(8):626.
doi: 10.3390/gels9080626.

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity

Sunitha Kumari  1 , Omar Awad Alsaidan  2 , Dibyalochan Mohanty  1 , Ameeduzzafar Zafar  2 , Swagatika Das  3 , Jeetendra Kumar Gupta  4 , Mohammad Khalid  5
Affiliations

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity

Sunitha Kumari et al. Gels. .

Abstract

Luliconazole (LZ) is a good candidate for the treatment of fungal infection topically but has limitations, i.e., poor solubility and poor permeability to skin. Due to these limitations, multiple administrations for a long time are required to treat the inflection. The aim of the present study was to develop the invasomes (IVS) gel of LZ to improve the topical antifungal activity. The IVS was prepared by the thin-film hydration method and optimized by Box-Bhekhen design software. The optimized LZIVS (LZIVSopt) has 139.1 ± 4.32 nm of vesicle size, 88.21 ± 0.82% of entrapment efficiency, 0.301 ± 0.012 of PDI, and 19.5 mV (negative) of zeta potential. Scanning microscopy showed a spherical shape of the vesicle. FTIR spectra showed there is no interaction between the drug and lipid. Thermogram showed that the LZ is encapsulated into the LZIVS matrix. LZIVSopt gel (LZIVSopt-G3) exhibited optimum viscosity (6493 ± 27 cps) and significant spreadability (7.2 g·cm/s). LZIVSopt-G3 showed 2.47-fold higher permeation than pure LZ-gel. LZIVSopt-G3 did not show any edema or swelling in the skin, revealing that the developed formulation is non-irritant. LZIVSopt-G3 exhibited significant inhibition of the fungus infection (C. albicans) in the infected rats. The finding concluded that IVS gel is a good carrier and an attractive approach for the enhancement of topical delivery of LZ to treat the fungal infection.

Keywords: antifungal activity; ex vivo skin permeation; invasomes gel; luliconazole; transdermal delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Response surface plots explaining the effect of citronella oil, soy lecithin, and sonication time over the vesicle size of invasomes. Citronella oil and soy lecithin showed positive effects, and sonication time showed negative effects on the vesicle size.
Figure 2
Figure 2
Response surface plots explaining the effect of citronella oil, soy lecithin, and sonication time over the entrapment efficiency of LZ in invasomes. Citronella oil and soy lecithin showed positive effects, and sonication time showed negative effects on the entrapment efficiency of LZ in invasomes.
Figure 3
Figure 3
Response surface plots explaining the effect of citronella oil, soy lecithin, and sonication time over the PDI of invasomes. Citronella oil and soy lecithin showed positive effects, and sonication time showed negative effects on the PDI of vesicle size.
Figure 4
Figure 4
(A) Vesicle size and its distribution, (B) zeta potential graph, and (C) SEM image of the optimized invasomes (LZIVSopt).
Figure 5
Figure 5
FTIR spectra of (A) pure LZ and (B) optimized formulation (LZIVSopt).
Figure 6
Figure 6
DSC spectra of (A) pure LZ showing a sharp endothermic peak at melting point (150.40 °C) and, (B) optimized formulation (LZIVSopt) did not show a peak of LZ (different colors explain the peaks).
Figure 7
Figure 7
Ex vivo permeation study graph of the different formulations using excised rat skin through Franz diffusion cell.
Figure 8
Figure 8
The irritation study of (A) control: without treatment, (B) treated with 0.9% sodium chloride, and (C) treated with optimized formulation (LZIVSopt) in albino Wistar rats.
Figure 9
Figure 9
In vitro antifungal activity against C. albicans of LZIVSopt-G3 and compared with pure LZ-gel and infected control. The figure showed the concentration of C. Albicans at different time intervals. ## (p < 0.01) compared with pure LZ-gel, *** (p < 0.001) compared with infected control.
See this image and copyright information in PMC

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