Thermosensitive hybrid hydrogels for the controlled release of bioactive vancomycin in the treatment of orthopaedic implant infections

Roberta Censi, Cristina Casadidio, Alessandra Dubbini, Manuela Cortese, Stefania Scuri, Iolanda Grappasonni, Samuel Golob, Dario Vojnovic, Maria Giovanna Sabbieti, Dimitrios Agas, Piera Di Martino*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The purpose of this work was the development of antibacterial delivery systems for vancomycin, with potential application in the prevention or treatment of orthopedic implant infections. Previous studies have shown tandem thermal gelling and Michael addition cross-linking of hydrogels based on methacrylate, acrylate or vinylsulfone triblock copolymers of PEG-p(HPMAm-lac1-2) and thiolated hyaluronic acid. In this work we exploited these α-β unsaturated derivatives of PEG-p(HPMAm-lac1-2) triblock copolymers and used them in combination with thiolated hyaluronic acid as controlled delivery systems for vancomycin. It was found that the antibiotic was sustainably released from the hydrogel networks for at least 5 days with release kinetics depending on diffusion and dissociation of the positively charged vancomycin from the negatively charged hyaluronic acid. The release of vancomycin could be tailored mainly by HA-SH solid content and degree of thiolation. The developed hydrogels were demonstrate efficacious in preserving the structural and functional integrity of the encapsulated drug by physical immobilization within the gel network and ionic interaction with hyaluronic acid, thereby preventing vancomycin deamidation processes. Furthermore, the antimicrobial activity of vancomycin loaded hydrogels was assessed, demonstrating retention of inhibitory activity towards Staphylococcus aureus during formulation and release, with slightly increased activity of vancomycin encapsulated in hydrogels of higher HA-SH content as compared to controls.

Original languageEnglish
Pages (from-to)322-333
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume142
DOIs
Publication statusPublished - 1 Sept 2019

Keywords

  • Controlled release
  • Michael addition cross-linking
  • Protein stability
  • Thermosensitive hydrogels
  • Vancomycin

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