Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections

Željka Vanić, Zora Rukavina, Suvi Manner, Adyary Fallarero, Lidija Uzelac, Marijeta Kralj, Daniela Amidžić Klarić, Anita Bogdanov, Tímea Raffai, D. Virók, Jelena Filipović-Grčić, Nataša Škalko-Basnet

Research output: Contribution to journalArticle

Abstract

Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

Original languageEnglish
Pages (from-to)5957-5976
Number of pages20
JournalInternational journal of nanomedicine
Volume14
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Azithromycin
Liposomes
Bacterial Infections
Biofilms
Escherichia coli
Antibiotics
Therapeutics
Propylene Glycol
Chlamydia trachomatis
Anti-Bacterial Agents
Glycols
Pharmaceutical Preparations
Propylene
Tissue
Chlamydia Infections
Macrolides
Elasticity
Cytotoxicity
Surface charge
Sexually Transmitted Diseases

Keywords

  • Biocompatibility
  • Biofilm
  • Cervical cells
  • Chlamydia trachomatis
  • Escherichia coli
  • Vaginal drug delivery

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Vanić, Ž., Rukavina, Z., Manner, S., Fallarero, A., Uzelac, L., Kralj, M., ... Škalko-Basnet, N. (2019). Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections. International journal of nanomedicine, 14, 5957-5976. https://doi.org/10.2147/IJN.S211691

Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections. / Vanić, Željka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klarić, Daniela Amidžić; Bogdanov, Anita; Raffai, Tímea; Virók, D.; Filipović-Grčić, Jelena; Škalko-Basnet, Nataša.

In: International journal of nanomedicine, Vol. 14, 01.01.2019, p. 5957-5976.

Research output: Contribution to journalArticle

Vanić, Ž, Rukavina, Z, Manner, S, Fallarero, A, Uzelac, L, Kralj, M, Klarić, DA, Bogdanov, A, Raffai, T, Virók, D, Filipović-Grčić, J & Škalko-Basnet, N 2019, 'Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections', International journal of nanomedicine, vol. 14, pp. 5957-5976. https://doi.org/10.2147/IJN.S211691
Vanić, Željka ; Rukavina, Zora ; Manner, Suvi ; Fallarero, Adyary ; Uzelac, Lidija ; Kralj, Marijeta ; Klarić, Daniela Amidžić ; Bogdanov, Anita ; Raffai, Tímea ; Virók, D. ; Filipović-Grčić, Jelena ; Škalko-Basnet, Nataša. / Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections. In: International journal of nanomedicine. 2019 ; Vol. 14. pp. 5957-5976.
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