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Pharmaceutical Research

, 35:187 | Cite as

Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa

  • Shaoning Wang
  • Shihui Yu
  • Yuwei Lin
  • Peizhi Zou
  • Guihong Chai
  • Heidi H. Yu
  • Hasini Wickremasinghe
  • Nivedita Shetty
  • Junhong Ling
  • Jian Li
  • Qi (Tony) Zhou
Research Paper
Part of the following topical collections:
  1. Nanomedicine for Infectious Diseases

Abstract

Purpose

This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.

Methods

Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.

Results

The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies.

Conclusions

Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.

KEY WORDS

antimicrobial activities ciprofloxacin colistin cytotoxicity in vitro release liposome Pseudomonas aeruginosa 

Abbreviations

AL

Anionic liposomes

Blank-AL

Blank anionic liposomes

Cip/Col-AL

Ciprofloxacin/Colistin anionic liposomes

Cip/Col-NL

Ciprofloxacin/Colistin neutral liposomes

Cip-AL

Ciprofloxacin anionic liposomes

Cipro

Ciprofloxacin hydrochloride monohydrate

Col

Colistin sulfate

Col-AL

Colistin anionic liposomes

Col-LUVs

Colistin-loaded unilamellar liposomes

cryo-TEM

Cryogenic transmission electron microscopy

MDR

Multidrug-resistant

MWCO

Molecular weight cut off

NL

Neutral liposomes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shaoning Wang
    • 1
    • 2
  • Shihui Yu
    • 2
    • 3
  • Yuwei Lin
    • 4
  • Peizhi Zou
    • 2
  • Guihong Chai
    • 2
  • Heidi H. Yu
    • 4
  • Hasini Wickremasinghe
    • 4
  • Nivedita Shetty
    • 2
  • Junhong Ling
    • 1
    • 2
  • Jian Li
    • 4
  • Qi (Tony) Zhou
    • 2
  1. 1.Department of Medicinal Chemistry, School of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyangChina
  2. 2.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA
  3. 3.Department of Pharmaceutics, School of PharmacyShenyang Pharmaceutical UniversityShenyangChina
  4. 4.Monash Biomedicine Discovery Institute, Department of MicrobiologyMonash UniversityClaytonAustralia

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