pH/Hyal-Responsive Surface-Charge Switchable Electrostatic Complexation for Efficient Elimination of MRSA Infection

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Antimicrobial Research

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat, necessitating innovative antibacterial strategies.
• Existing treatments face challenges in efficacy and targeted delivery, driving the need for advanced therapeutic systems.

Purpose of the Study:

• To develop a cationic pH-responsive delivery system (pHSM) encapsulating linezolid (LZD) for enhanced MRSA treatment.
• To improve system stability and targeting by surface-functionalizing with low-molecular-weight hyaluronic acid (LWT HA), forming pHSM/LZD@HA.
• To investigate the pH and hyaluronidase (Hyal)-dependent properties of pHSM/LZD@HA for improved bacterial binding, biofilm penetration, and drug release.

Main Methods:

• Fabrication of a poly(β-amino esters)-methoxy poly(ethylene glycol)-based cationic pH-responsive system (pHSM).
• Encapsulation of linezolid (LZD) into pHSM, followed by surface modification with LWT HA to form pHSM/LZD@HA.
• Evaluation of surface charge changes under acidic conditions and in the presence of hyaluronidase (Hyal).
• Assessment of bacterial binding, biofilm penetration, and drug release kinetics in vitro and in vivo.

Main Results:

• The pHSM/LZD@HA system exhibited neutralized surface charges at physiological pH, which rapidly shifted to positive under acidic conditions (pH ≤ 0.5 h).
• The presence of Hyal accelerated the surface charge transition and enhanced biofilm penetration.
• A pH/Hyal-dependent accelerated drug release profile was observed, correlating with improved MRSA treatment outcomes.
• The developed system demonstrated good biocompatibility and stability.

Conclusions:

• The study presents a novel pH/Hyal-responsive drug delivery system (pHSM/LZD@HA) for effective MRSA infection treatment.
• The system's ability to respond to acidic environments and hyaluronidase facilitates targeted drug delivery and enhanced therapeutic efficacy.
• This strategy offers a promising approach for developing advanced antimicrobial therapies against challenging bacterial infections.