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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
Published on: February 7, 2021
Controlled Delivery of Vancomycin via Charged Hydrogels
Carl T Gustafson1, Felix Boakye-Agyeman2, Cassandra L Brinkman3
1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55902, United States of America.
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.
Insights
New hydrogel formulations offer localized, controlled release of vancomycin to prevent surgical site infections (SSI). This approach enhances antibiotic effectiveness and reduces systemic side effects for orthopedic surgery patients.
Area of Science:
- Biomaterials Science
- Infectious Disease Research
- Drug Delivery Systems
Background:
- Surgical site infections (SSI) pose a significant risk in orthopedic surgery, often necessitating further interventions and prolonging recovery.
- Current antimicrobial strategies for SSI prophylaxis face limitations including systemic toxicity, bacterial resistance, and poor patient compliance.
- Localized, controlled-release antibiotic formulations are needed to improve efficacy and minimize adverse effects.
Purpose of the Study:
- To engineer biocompatible oligo(poly(ethylene glycol)fumarate)/sodium methacrylate (OPF/SMA) charged copolymers as hydrogel matrices for localized antibiotic delivery.
- To characterize the vancomycin loading capacity and release kinetics of the developed OPF/SMA hydrogels.
- To evaluate the antimicrobial efficacy of vancomycin released from the hydrogel against methicillin-resistant Staphylococcus aureus (MRSA).
Main Methods:
- Development and characterization of OPF/SMA charged copolymers as hydrogel matrices.
- Loading of vancomycin into the hydrogel, assessing time- and charge-dependency.
- Measurement of vancomycin release kinetics over time.
- Assessment of the antimicrobial activity of released vancomycin against a clinical MRSA strain.
Main Results:
- OPF/SMA hydrogels demonstrated efficient vancomycin loading (over 500 μg/mg), dependent on time and charge.
- Vancomycin release kinetics were modulated by copolymer negative charge, with controlled release observed over four days.
- Released vancomycin retained antimicrobial activity equivalent to stock vancomycin against MRSA.
- Controlled release achieved low initial release rates (33.7% in 6 hours, <80% in 24 hours).
Conclusions:
- Engineered OPF/SMA hydrogels show promise as effective carriers for localized antibiotic delivery.
- This localized delivery system can potentially improve prophylaxis of surgical site infections.
- The developed hydrogels offer a strategy to enhance antibiotic treatment effectiveness while mitigating systemic side effects.
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