Proton-mediated burst of dual-drug loaded liposomes for biofilm dispersal and bacterial killing

Da Yuan Wang, Guang Yang, Xiao-Xiao Zhang, Henny C. van der Mei*, Yijin Ren, Henk J. Busscher, Linqi Shi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Exposure of infectious biofilms to dispersants induces high bacterial concentrations in blood that may cause sepsis. Preventing sepsis requires simultaneous biofilm dispersal and bacterial killing. Here, self-targeting DCPA(2-(4-((1,5-bis(octadecenoyl)1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water were self-assembled with ciprofloxacin loaded in-membrane and PEGylated as a lipid-membrane component, together with bromelain loaded in-core. Inside biofilms, DCPA-H2O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid-membrane to cause liposome-burst and simultaneous release of bromelain and ciprofloxacin. Simultaneous release of bromelain and ciprofloxacin enhanced bacterial killing in Staphylococcus aureus biofilms as compared with free bromelain and/or ciprofloxacin. After tail-vein injection in mice, liposomes accumulated inside intra-abdominal staphylococcal biofilms. Subsequent liposome-burst and simultaneous release of bromelain and ciprofloxacin yielded degradation of the biofilm matrix by bromelain and higher bacterial killing without inducing septic symptoms as obtained by injection of free bromelain and ciprofloxacin. This shows the advantage of simultaneous release from liposomes of bromelain and ciprofloxacin inside a biofilm.

Original languageEnglish
Pages (from-to)460-471
Number of pages12
JournalJournal of Controlled Release
Publication statusPublished - Dec-2022


  • Bromelain
  • Ciprofloxacin
  • Dual-drug loaded
  • In vivo
  • Prevention of sepsis
  • Self-targeting
  • Staphylococcus aureus

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