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. 2023 Apr 28;15(5):1356.
doi: 10.3390/pharmaceutics15051356.

A Novel Approach for the Treatment of Aerobic Vaginitis: Azithromycin Liposomes-in-Chitosan Hydrogel

Ana Čačić  1 , Daniela Amidžić Klarić  2 , Sabina Keser  2 , Maja Radiković  2 , Zora Rukavina  2 , May Wenche Jøraholmen  3 , Lidija Uzelac  4 , Marijeta Kralj  4 , Nataša Škalko-Basnet  3 , Maja Šegvić Klarić  5 , Željka Vanić  2
Affiliations

A Novel Approach for the Treatment of Aerobic Vaginitis: Azithromycin Liposomes-in-Chitosan Hydrogel

Ana Čačić et al. Pharmaceutics. .

Abstract

Biocompatible mucoadhesive formulations that enable a sustained drug delivery at the site of action, while exhibiting inherent antimicrobial activity, are of great importance for improved local therapy of vaginal infections. The aim of this research was to prepare and evaluate the potential of the several types of azithromycin (AZM)-liposomes (180-250 nm) incorporated into chitosan hydrogel (AZM-liposomal hydrogels) for the treatment of aerobic vaginitis. AZM-liposomal hydrogels were characterized for in vitro release, and rheological, texture, and mucoadhesive properties under conditions simulating the vaginal site of application. The role of chitosan as a hydrogel-forming polymer with intrinsic antimicrobial properties was explored against several bacterial strains typical for aerobic vaginitis as well as its potential effect on the anti-staphylococcal activity of AZM-liposomes. Chitosan hydrogel prolonged the release of the liposomal drug and exhibited inherent antimicrobial activity. Additionally, it boosted the antibacterial effect of all tested AZM-liposomes. All AZM-liposomal hydrogels were biocompatible with the HeLa cells and demonstrated mechanical properties suitable for vaginal application, thus confirming their potential for enhanced local therapy of aerobic vaginitis.

Keywords: aerobic vaginitis; antimicrobial activity; azithromycin; chitosan; hydrogel; liposomes; vaginal drug delivery; vaginal infections.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
pH values of the originally prepared chitosan-HG and different AZM-hydrogels. The results represent the mean ± S.D. (n = 3). CLs-HG, conventional AZM-liposomes-in-chitosan-HG; control-HG, AZM-solution-in-chitosan-HG; DPGLs-HG, deformable propylene glycol AZM-liposomes-in-chitosan-HG; PGLs-HG, propylene glycol AZM-liposomes-in-chitosan-HG.
Figure 2
Figure 2
Cumulative in vitro release of AZM from the different AZM-hydrogels. The values represent the mean ± S.D. (n = 3). * Significantly different compared to control-HG at the 24 h time point (p < 0.05). ** Significantly different from DPGLs-HG at the 24 h time point (p < 0.05).
Figure 3
Figure 3
Viscosity profiles of different AZM-liposomal hydrogels at 25 °C and mimicked vaginal conditions (+VFS, 37 °C).
Figure 4
Figure 4
Amplitude sweep curves of the different AZM-liposomal hydrogels under mimicked vaginal conditions (+VFS, 37 °C).
Figure 5
Figure 5
Texture properties of the different hydrogels, expressed as hardness and cohesiveness. * Force (g) refers to the hardness, while Area (g × s) refers to the cohesiveness. The presented values are the mean ± S.D. (n = 5). ** Significantly different compared to the chitosan-HG (p < 0.05).
Figure 6
Figure 6
Mucoadhesion of different AZM-hydrogels on porcine vaginal mucosa: force detachment values (A) and work of adhesion (B). The values are the mean ± S.D. (n = 3). * Significantly different (p < 0.05).
Figure 7
Figure 7
HeLa cell viability after incubation with the different AZM-hydrogels, expressed by AZM concentration (A), and with the corresponding AZM-free hydrogels (B). The presented values are the mean ± S.D. (n = 3).
Figure 7
Figure 7
HeLa cell viability after incubation with the different AZM-hydrogels, expressed by AZM concentration (A), and with the corresponding AZM-free hydrogels (B). The presented values are the mean ± S.D. (n = 3).
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