Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin

Abstract

Context: Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs.

Objectives: This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability.

Methods: Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug–excipient interaction using zetasizer, atomic force microscope (AFM), LC–MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits.

Results: The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits.

Conclusions: The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Keywords:

• Creatinine
• nonionic surfactant
• niosomes
• Azithromycin
• bioavailability

Acknowledgements

All the authors are thankful to Mr. Bilal Ahmad and Miss Sehrosh Khan, LC–MS/MS analysts, Center for Bioequivalence and Clinical Research (CBCR), for their help in bioavailability study. MR Shah is thankful to Organization of Prohibition of Chemical Weapons for financial support of project No: L/ICA/ICB/194480/14.

Disclosure statement

The authors state that they have no conflicts of interests to disclose.

Additional information

Funding

Shafi Ullah is thankful to Higher Education Commission, Pakistan, for providing him PhD scholarship (PIN: 213-61444-2BM2-050).