Surfactant-enriched liposomes to enhance azithromycin efficacy in Chlamydia trachomatis infections

Chlamydia trachomatis is responsible for the most common bacterial sexually transmitted infection. Oral administration of azithromycin (AZT) represents the first-line treatment. However, AZT shows a low oral bioavailability, due to its poor aqueous solubility, high degradation in the stomach and incomplete absorption. To address these problems, this study aimed to develop vaginal surfactant-enriched liposomes (LP), specifically designed to improve penetration through the mucus barrier, covering the vaginal epithelium. AZT-loaded LP were prepared through the ethanol injection technique by using phosphatidylcholine in association with surfactants from the Span or Tween series. LP were characterised in terms of size, surface charge, encapsulation efficiency, stability, in vitro AZT release, morphology and mucopenetrating properties. Cytotoxicity on HeLa cells and antimicrobial activity against C. trachomatis were also assessed. LP presented different diameters and ζ-potential depending on the type of surfactant. All the formulations presented a spherical shape and were characterized by a good capacity to encapsulate AZT. Moreover, among all the formulations, Tween 80 and Span 20-containing LP provided the best AZT release profiles and were distinguished by good mucopenetrating properties. Furthermore, they remained stable over a six-month storage period. Finally, the selected LP did not show significant alteration in terms of HeLa cell viability, determining at the same time a slightly enhanced antimicrobial activity against C. trachomatis compared to free AZT. In conclusion, the developed formulations could be proposed as a promising platform for the local treatment of C. trachomatis infections, contributing to the progress in vaginal drug delivery.