Liposomes-In-Hydrogel Delivery System Enhances the Potential of Resveratrol in Combating Vaginal Chlamydia Infection

Abstract

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections and causes serious reproductive tract complications among women. The limitations of existing oral antibiotics and treatment of antimicrobial resistance require alternative treatment options. We are proposing, for the first time, the natural polyphenol resveratrol (RES) in an advanced delivery system comprising liposomes incorporated in chitosan hydrogel, for the localized treatment of C. trachomatis infection. Both free RES and RES liposomes-in-hydrogel inhibited the propagation of C. trachomatis in a concentration-dependent manner, assessed by the commonly used in vitro model comprising McCoy cells. However, for lower concentrations, the anti-chlamydial effect of RES was enhanced when incorporated into a liposomes-in-hydrogel delivery system, with inhibition of 78% and 94% for 1.5 and 3 µg/mL RES, respectively for RES liposomes-in-hydrogel, compared to 43% and 72%, respectively, for free RES. Furthermore, RES liposomes-in-hydrogel exhibited strong anti-inflammatory activity in vitro, in a concentration-dependent inhibition of nitric oxide production in the LPS-induced macrophages (RAW 264.7). The combination of a natural substance exhibiting multi-targeted pharmacological properties, and a delivery system that provides enhanced activity as well as applicability for vaginal administration, could be a promising option for the localized treatment of C. trachomatis infection.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…Superior antichlamydial activity in vitro was by resveratrol liposomes-in-hydrogel in the lower concentrations [276] Vaginal film…”

“…Chlamydia trachomatis is a small obligate intracellular, Gram-negative bacterium that is the most common cause of bacterial STIs [276], with an estimated annual incidence of 127 million new infections globally [277]. Moreover, due to the asymptomatic nature of C. trachomatis infections, the number is believed to be considerably underestimated.…”

“…The combination of two delivery systems, a drug nanocarrier incorporated into a chitosan hydrogel, has recently been evaluated for its antibacterial effect, namely the liposome-in-hydrogel delivery system. Jøraholmen et al aimed to prove the in vitro antichlamydial effect of natural substance resveratrol in a suitable delivery system [276]. C. trachomatis infected cells were exposed to free resveratrol, liposomal resveratrol, resveratrol liposomes-in-hydrogel and respective controls free of resveratrol.…”

Antimicrobial Polymer-Based Hydrogels for the Intravaginal Therapies—Engineering Considerations

“…Their introduction into the structure of the hydrogel system not only ensures the incorporation of a substantial amount of hydrophobic drug into the hydrogel material and prolonged contact time at the site of drug action, but the release rate can be also adjusted with the properties of both carriers. Amongst particles applied for the enhancement of vaginal treatment, nanosponges [28,44], liposomes [45,46], nanocapsules [35], and solid particles [6], etc., can be distinguished.…”

In Vitro Modelling of Chlamydia trachomatis Infection in the Etiopathogenesis of Male Infertility and Reactive Arthritis

“…The ample spectrum of diseases caused by C. trachomatis infection is reflected in its ability to infect and multiply within a wide range of different cell types, such as cervical epithelial cells, peripheral blood mononuclear cells (Dolat and Valdivia, 2019;Lausen et al, 2019). The typical model of chlamydial intracellular development has been mostly investigated in human cervical epithelial cells (HeLa) and murine fibroblasts (McCoy), for which C. trachomatis possesses the highest tropism (Belland et al, 2003;Guseva et al, 2007;Vromman et al, 2014;Petyaev et al, 2017;Sessa et al, 2017a;Filardo et al, 2019a;Liang and Mahony, 2019;Jøraholmen et al, 2020). C. trachomatis developmental cycle occurs entirely within a cell-derived membrane bound vesicle termed inclusion, where Chlamydiae alternate between the elementary body (EB), the extracellular and infectious form, and the reticulate body (RB), the metabolically active form, responsible for intracellular replication (AbdelRahman and Belland, 2005).…”