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Antibacterial Micelles with Vancomycin-Mediated Targeting and pH/Lipase-Triggered Release of Antibiotics

Maohua Chen1, Songzhi Xie1, Jiaojun Wei1

  • 1Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering , Southwest Jiaotong University , Chengdu 610031 , P. R. China.

ACS Applied Materials & Interfaces
|October 10, 2018
PubMed

Insights

This study developed novel micelle carriers that target bacteria using vancomycin (VAN) and sequentially release VAN and ciprofloxacin (CIP) antibiotics on demand. This enhanced antibiotic delivery improved survival and reduced bacterial burden in infected mice.

Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Infectious Disease Therapeutics

Background:

  • Antibiotic delivery systems are crucial for enhancing efficacy and combating resistance.
  • Few systems achieve targeted bacterial delivery and on-demand antibiotic release, despite shared pathways with tumor tissues.

Purpose of the Study:

  • To develop and evaluate amphiphilic copolymer micelles conjugated with vancomycin (VAN) for targeted bacterial delivery and sequential antibiotic release.
  • To investigate the efficacy of these micelles in treating Pseudomonas aeruginosa infections in a mouse model.

Main Methods:

  • Conjugation of vancomycin (VAN) to poly(ethylene glycol)-poly(ε-caprolactone) (PECL) copolymers via pH-cleavable hydrazone bonds to form micelle carriers (Van-hyd-PECL).
  • Encapsulation of ciprofloxacin (CIP) into Van-hyd-PECL micelles.
  • In vitro characterization of micelle size and drug loading.
  • In vivo evaluation of micelle efficacy in Pseudomonas aeruginosa-infected mice, assessing survival rates, bacterial burdens, and lung injury.

Main Results:

  • Van-hyd-PECL/Cip micelles (77 nm size, 4.5% CIP loading) demonstrated enhanced blood circulation and selective bacterial recognition.
  • Acidic conditions at infection sites triggered VAN release, increasing micelle size and facilitating lipase-mediated degradation and subsequent CIP release.
  • Micelle treatment significantly improved survival, reduced bacterial load, and mitigated lung injury in infected mice compared to free drugs or non-targeted micelles.
  • Multiple doses further enhanced survival and restored lung microstructure.

Conclusions:

  • A novel strategy was developed for enhanced bacterial targeting using antibiotic-conjugated micelles.
  • The system enables sequential, on-demand release of two antibiotics (VAN and CIP) at the infection site.
  • This approach holds promise for improving the treatment of bacterial infections and overcoming antibiotic resistance.
Keywords:
acid-liable deshieldingantibiotics-loaded micellein vivo antibacterial efficacylipase-sensitive releasevancomycin-mediated targeting

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