Controlled Delivery of Vancomycin via Charged Hydrogels

Abstract

Surgical site infection (SSI) remains a significant risk for any clean orthopedic surgical procedure. Complications resulting from an SSI often require a second surgery and lengthen patient recovery time. The efficacy of antimicrobial agents delivered to combat SSI is diminished by systemic toxicity, bacterial resistance, and patient compliance to dosing schedules. We submit that development of localized, controlled release formulations for antimicrobial compounds would improve the effectiveness of prophylactic surgical wound antibiotic treatment while decreasing systemic side effects. Our research group developed and characterized oligo(poly(ethylene glycol)fumarate) / sodium methacrylate (OPF/SMA) charged copolymers as biocompatible hydrogel matrices. Here, we report the engineering of this copolymer for use as an antibiotic delivery vehicle in surgical applications. We demonstrate that these hydrogels can be efficiently loaded with vancomycin (over 500 μg drug per mg hydrogel) and this loading mechanism is both time- and charge-dependent. Vancomycin release kinetics are shown to be dependent on copolymer negative charge. In the first 6 hours, we achieved as low as 33.7% release. In the first 24 hours, under 80% of total loaded drug was released. Further, vancomycin release from this system can be extended past four days. Finally, we show that the antimicrobial activity of released vancomycin is equivalent to stock vancomycin in inhibiting the growth of colonies of a clinically derived strain of methicillin-resistant Staphylococcus aureus. In summary, our work demonstrates that OPF/SMA hydrogels are appropriate candidates to deliver local antibiotic therapy for prophylaxis of surgical site infection.

Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications

“…This suggest a strong binding of the drug to the negatively charged hydrogel backbone. This behaviour has been described in the literature before for the release of positively charged drugs from polymeric matrices containing negative charges ( Gustafson et al, 2015 ; Korogiannaki, Guidi, Jones, & Sheardown, 2015 ). Consequently, due to its higher fluid uptake and better release properties, 5H1G seems to be the most promising hydrogel for wound dressing applications.…”

Antibacterial Hydrogels

“…The charged hydrogel, which was loaded with VAN over 500 µg mg −1 hydrogel, was able to control the VAN delivery and was used to combat the surgical site infections against MRSA ( Figure 7 ). 80 Development of an injectable gellan gum‐based PLGA NP‐loaded system,81 injectable Pluronic–α‐CD supramolecular gels (CD, cyclodextrin),82 and hydrogels consisting of thiolated chitosan crosslinked with maleic acid‐grafted dextran83 provided new opportunities for antimicrobial research. The photo‐crosslinked methacrylated dextran and poly( l ‐glutamic acid)‐ graft ‐hydroxyethyl methacrylate (PGA‐ g ‐HEMA) hydrogels were studied84 and both exhibited excellent antibacterial properties and desirable release capabilities.…”

“…Gustafson et al developed a charged hydrogel as a carrier. The charged hydrogel, which was loaded with VAN over 500 µg mg −1 hydrogel, was able to control the VAN delivery and was used to combat the surgical site infections against MRSA ( Figure ) . Development of an injectable gellan gum‐based PLGA NP‐loaded system, injectable Pluronic–α‐CD supramolecular gels (CD, cyclodextrin), and hydrogels consisting of thiolated chitosan crosslinked with maleic acid‐grafted dextran provided new opportunities for antimicrobial research.…”

Antimicrobial hydrogels: promising materials for medical application

“…[158][159][160] As mentioned earlier, hydrogels as a delivery system are able to protect and enhance the validity of vancomycin. Syringeable pluronic-α-cyclodextrin (CD) supramolecular gels, 161 hydrogel of thiolated CS cross-linked with maleic acid-grafted dextrin, 162 thermosensitive hydrogel of CS/gelatin/β-glycerol phosphate, 163 hydrogel of oligo(PEG fumarate)/sodium methacrylate (OPF/SMA) charged copolymers as biocompatible matrices, 164 poly(β-amino ester) (PBAE) hydrogels mixed with PEG (MW = 400) diacrylate (PEGDA) and diethylene glycol diacrylate (DEGDA) 165 and hydrogels achieved by photo cross-linking of methacrylated dextran and poly(l-glutamic acid)-g-hydroxyethyl methacrylate are all studied, and they exhibited excellent antimicrobial properties and desirable release capacity. 166 The most common pathogen of osteomyelitis is S. aureus, especially MRSA.…”