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Abstract <p>This study reports the development of a novel pH-responsive hybrid nanocomposite for the targeted delivery of ciprofloxacin. The system is based on amorphous calcium carbonate nanoparticles stabilized by a biocompatible glucamine-modified resorcinarene–boronate polymer. The polymer shell was engineered via interfacial polycondensation within a triolein-in-water microemulsion, utilizing dynamic boronate ester crosslinks to ensure a pH-sensitive architecture. Ciprofloxacin was encapsulated <i>in situ</i>, followed by the controlled precipitation of calcium carbonate. The resulting CaCO<sub>3</sub>@Cipro@p(Glc-B) nanoparticles exhibited a spherical morphology (40–60 nm by TEM/AFM) with high colloidal stability (ζ = –54 mV). Crucially, the release of ciprofloxacin was accelerated under mildly acidic conditions (41% at pH 6.5 vs. 24% at pH 7.0), resembling the acidic environment of inflammation. Antibacterial assays demonstrated a remarkable strain-dependent potentiation of ciprofloxacin. While activity against Gram-positive strains was preserved, the nanocomposite showed a 4-fold increase in efficacy against <i>E. coli</i> (MIC decreased from 0.09 to 0.024 μM) and a 2-fold increase against <i>P. aeruginosa</i>. Notably, the nanoformulation drastically enhanced bactericidal efficiency against <i>B. cereus</i>, reducing the MBC four-fold (from 50.8 to 12.7 μM). With the polymer scaffold being non-toxic up, these findings suggest that combining pH-responsive boronate networks with calcium carbonate provides a powerful strategy to overcome the limitations of conventional antibiotics against Gram-negative pathogens.</p>

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Hybrid Nanocomposites of Calcium Carbonate and Glucamine-Modified Resorcinarene-Boronate Polymer: Synthesis, Characterization, and Antibacterial Activity

  • 期刊论文

  • 发表日期：

    2026年4月22日

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  • Amir A. Shamsutdinov,
  • Andrey A. Maslennikov,
  • Elina E. Mansurova,
  • Anna P. Lyubina,
  • Anastasia S. Sapunova,
  • Alexandra D. Voloshina,
  • Guliya R. Nizameeva,
  • Irek R. Nizameev,
  • Kirill V. Kholin,
  • Aidar T. Gubaidullin,
  • Albina Y. Ziganshina,
  • Igor S. Antipin

摘要

Abstract

This study reports the development of a novel pH-responsive hybrid nanocomposite for the targeted delivery of ciprofloxacin. The system is based on amorphous calcium carbonate nanoparticles stabilized by a biocompatible glucamine-modified resorcinarene–boronate polymer. The polymer shell was engineered via interfacial polycondensation within a triolein-in-water microemulsion, utilizing dynamic boronate ester crosslinks to ensure a pH-sensitive architecture. Ciprofloxacin was encapsulated in situ, followed by the controlled precipitation of calcium carbonate. The resulting CaCO3@Cipro@p(Glc-B) nanoparticles exhibited a spherical morphology (40–60 nm by TEM/AFM) with high colloidal stability (ζ = –54 mV). Crucially, the release of ciprofloxacin was accelerated under mildly acidic conditions (41% at pH 6.5 vs. 24% at pH 7.0), resembling the acidic environment of inflammation. Antibacterial assays demonstrated a remarkable strain-dependent potentiation of ciprofloxacin. While activity against Gram-positive strains was preserved, the nanocomposite showed a 4-fold increase in efficacy against E. coli (MIC decreased from 0.09 to 0.024 μM) and a 2-fold increase against P. aeruginosa. Notably, the nanoformulation drastically enhanced bactericidal efficiency against B. cereus, reducing the MBC four-fold (from 50.8 to 12.7 μM). With the polymer scaffold being non-toxic up, these findings suggest that combining pH-responsive boronate networks with calcium carbonate provides a powerful strategy to overcome the limitations of conventional antibiotics against Gram-negative pathogens.