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. 2025 Apr 27;11(5):326.
doi: 10.3390/gels11050326.

Formulation of Caffeine-Hydroxypropyl-β-Cyclodextrin Complex in Hydrogel for Skin Treatment

Lyubomira Radeva  1 , Eleftheria Kalampalika  1 , Yordan Yordanov  1 , Petar D Petrov  2 , Virginia Tzankova  1 , Krassimira Yoncheva  1
Affiliations

Formulation of Caffeine-Hydroxypropyl-β-Cyclodextrin Complex in Hydrogel for Skin Treatment

Lyubomira Radeva et al. Gels. .

Abstract

Caffeine is a well-known xanthine that possesses antioxidant effects that could contribute to its application in different skin disorders. In order to enhance its effects, approaches for improving its permeation and penetration through skin layers could be applied. This study emphasizes the preparation of caffeine-cyclodextrin complex and its formulation in carbopol hydrogel. The complex was developed at a 1:1 molar ratio between caffeine and hydroxypropyl-β-cyclodextrin. It was found that the complex enhanced the radical scavenging activity of caffeine against ABTS radical as well as the protective effects against H2O2-induced oxidative stress in L929 fibroblasts. Then, the complex was formulated in hydrogel by applying 1% carbopol. The spreadability and penetration of the loaded hydrogel were improved in comparison with the empty hydrogel. The results revealed that the system could be appropriate for therapies of skin disorders, and its wound healing abilities could be further investigated.

Keywords: antioxidant activity; caffeine; complex; hydrogel; hydroxypropyl-β-cyclodextrin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Images of pure caffeine (1) and complexes (2, 3, 4, 5, 6 and 7) prepared at a ratio 1:1, 1:2, 1:3, 1:4, 1:5 and 1:6 between caffeine and hydroxypropyl-β-cyclodextrin, respectively.
Figure 2
Figure 2
Phase-solubility profile of caffeine incorporated in the hydroxypropyl-β-cyclodextrin complex.
Figure 3
Figure 3
Radical scavenging activity of pure caffeine (Caff) and caffeine incorporated into the complex (Caff-CD) against DPPH (a) and ABTS (b) radicals. ## p < 0.01 and ### p < 0.001 vs. DPPH and ABTS groups; * p < 0.05 and *** p < 0.001 between pure caffeine and caffeine incorporated into the complex.
Figure 4
Figure 4
Cytotoxic effects of caffeine on L929 fibroblasts; ** p < 0.01 and *** p < 0.001 vs. control (a) and protective effects of pure caffeine (Caff) and caffeine incorporated into the complex (Caff-CD) against H2O2-induced oxidative stress in L929 fibroblasts; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. H2O2-treated control (b).
Figure 5
Figure 5
Image of the Caff-CD hydrogel (a), spreadability (b), and penetrometry (c) of the empty hydrogel (empty HG) and the hydrogel loaded with caffeine complex (Caff-CD HG).
Figure 6
Figure 6
Variation in elastic (G′) and loss (G′′) moduli as a function of shear strain (a) and frequency (b).
Figure 7
Figure 7
In vitro dissolution profiles of caffeine from carbopol hydrogel loaded with caffeine complex (Caff-CD-HG) and pure caffeine (Caff) at pH = 5.0.
Figure 8
Figure 8
Schematic diagram of the preparation of carbopol hydrogel loaded with the caffeine–hydroxypropyl-β-cyclodextrin complex.
See this image and copyright information in PMC

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