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 output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number187
Number of pages13
JournalPharmaceutical Research
Volume35
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • antimicrobial activities
  • ciprofloxacin
  • colistin
  • cytotoxicity
  • in vitro release
  • liposome
  • Pseudomonas aeruginosa

Cite this

Wang, Shaoning ; Yu, Shihui ; Lin, Yuwei ; Zou, Peizhi ; Chai, Guihong ; Yu, Heidi H. ; Wickremasinghe, Hasini ; Shetty, Nivedita ; Ling, Junhong ; Li, Jian ; Zhou, Qi (Tony). / Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa. In: Pharmaceutical Research. 2018 ; Vol. 35, No. 10.
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title = "Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa",
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.",
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author = "Shaoning Wang and Shihui Yu and Yuwei Lin and Peizhi Zou and Guihong Chai and Yu, {Heidi H.} and Hasini Wickremasinghe and Nivedita Shetty and Junhong Ling and Jian Li and Zhou, {Qi (Tony)}",
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Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa. / Wang, Shaoning; Yu, Shihui; Lin, Yuwei; Zou, Peizhi; Chai, Guihong; Yu, Heidi H.; Wickremasinghe, Hasini; Shetty, Nivedita; Ling, Junhong; Li, Jian; Zhou, Qi (Tony).

In: Pharmaceutical Research, Vol. 35, No. 10, 187, 01.10.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa

AU - Wang, Shaoning

AU - Yu, Shihui

AU - Lin, Yuwei

AU - Zou, Peizhi

AU - Chai, Guihong

AU - Yu, Heidi H.

AU - Wickremasinghe, Hasini

AU - Shetty, Nivedita

AU - Ling, Junhong

AU - Li, Jian

AU - Zhou, Qi (Tony)

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - antimicrobial activities

KW - ciprofloxacin

KW - colistin

KW - cytotoxicity

KW - in vitro release

KW - liposome

KW - Pseudomonas aeruginosa

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DO - 10.1007/s11095-018-2464-8

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SN - 0724-8741

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