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<p>Dextran-based single chain polymeric nanoparticles (DXT-SCPN) were developed as drug delivery system to enhance inhalation-based antibiotic and improve biofilm penetration. The nanoparticles carry negative charges, allowing electrostatic interactions with positively-charged molecules at physiological pH. Apramycin (apry), a positively charged antibiotic, could interact with anionic DXT-SCPN. Here, we aimed at studying the effect of the main physico-chemical parameters of DXT-SCPN, i.e. degree of cross-linking (CL) and substitution (DS), on their interactions with apry. Thus, by adjusting the reaction parameters, DXT-SCPN were produced with CL at 5% and 15%, while DS could be adjusted at 25, 50 and 70%. The resulting nanoparticles exhibited hydrodynamic diameters comprised between 13 and 17&#xa0;nm with a polydispersity index of 0.26–0.32, while the number-averaged-diameter determined by Transmission Electron Microscopy was found to be 7–12&#xa0;nm. As expected, DS proved to affect significantly DXT-SCPN ζ-potential as higher number of anionic carboxylate groups, more negatively charged nanoparticles, resulted in higher amount of interactions with apry, from 20 to 40 wt% as DS increased. Surface tension studies have shown that all DXT-SCPN<sub>apry</sub> nano-formulation, except for lower DS, showed sufficient interfacial activity, from 59.34 to 62.07 mN/m, to anticipate good nebulization for future administration by inhalation. Finally, the higher cytocompatible concentration of the nano-formulation for A549, a lung cell line, was found to be around 10&#xa0;mg/mL. Altogether it was found that the nano-antibiotic with better stability and higher cytocompatibility was obtained for DXT-SCPN with DS at 50% and CL of 5% formulated with 30 wt% of apry.</p>

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Effect of the substitution and crosslinking degrees of dextran-based single-chain polymeric nanoparticles on their interactions with apramycin

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • José C. Ibáñez,
  • Julie Movellan,
  • Iraida Loinaz,
  • Jose M. Miramon,
  • Damien Dupin

摘要

Dextran-based single chain polymeric nanoparticles (DXT-SCPN) were developed as drug delivery system to enhance inhalation-based antibiotic and improve biofilm penetration. The nanoparticles carry negative charges, allowing electrostatic interactions with positively-charged molecules at physiological pH. Apramycin (apry), a positively charged antibiotic, could interact with anionic DXT-SCPN. Here, we aimed at studying the effect of the main physico-chemical parameters of DXT-SCPN, i.e. degree of cross-linking (CL) and substitution (DS), on their interactions with apry. Thus, by adjusting the reaction parameters, DXT-SCPN were produced with CL at 5% and 15%, while DS could be adjusted at 25, 50 and 70%. The resulting nanoparticles exhibited hydrodynamic diameters comprised between 13 and 17 nm with a polydispersity index of 0.26–0.32, while the number-averaged-diameter determined by Transmission Electron Microscopy was found to be 7–12 nm. As expected, DS proved to affect significantly DXT-SCPN ζ-potential as higher number of anionic carboxylate groups, more negatively charged nanoparticles, resulted in higher amount of interactions with apry, from 20 to 40 wt% as DS increased. Surface tension studies have shown that all DXT-SCPNapry nano-formulation, except for lower DS, showed sufficient interfacial activity, from 59.34 to 62.07 mN/m, to anticipate good nebulization for future administration by inhalation. Finally, the higher cytocompatible concentration of the nano-formulation for A549, a lung cell line, was found to be around 10 mg/mL. Altogether it was found that the nano-antibiotic with better stability and higher cytocompatibility was obtained for DXT-SCPN with DS at 50% and CL of 5% formulated with 30 wt% of apry.