Related Experiment Video
Updated: Feb 24, 2026
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Particle engineering for intracellular delivery of vancomycin to methicillin-resistant Staphylococcus aureus
Yihua Pei1, Mohamed F Mohamed2, Mohamed N Seleem3
1Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) infection is a serious threat to the public health. MRSA is particularly difficult to treat when it invades host cells and survive inside the cells. Although vancomycin is active against MRSA, it does not effectively kill intracellular MRSA due to the molecular size and polarity that limit its cellular uptake. To overcome poor intracellular delivery of vancomycin, we developed a particle formulation (PpZEV) based on a blend of polymers with distinct functions: (i) poly(lactic-co-glycolic acid) (PLGA, P) serving as the main delivery platform, (ii) polyethylene glycol-PLGA conjugate (PEG-PLGA, p) to help maintain an appropriate level of polarity for timely release of vancomycin, (iii) Eudragit E100 (a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, E) to enhance vancomycin encapsulation, and (iv) a chitosan derivative called ZWC (Z) to trigger pH-sensitive drug release. PpZEV NPs were preferentially taken up by the macrophages due to its size (500-1000nm) and facilitated vancomycin delivery to the intracellular pathogens. Accordingly, PpZEV NPs showed better antimicrobial activity than free vancomycin against intracellular MRSA and other intracellular pathogens. When administered intravenously, PpZEV NPs rapidly accumulated in the liver and spleen, the target organs of intracellular infection. Therefore, PpZEV NPs is a promising carrier of vancomycin for the treatment of intracellular MRSA infection.
Insights
New nanoparticles effectively deliver vancomycin inside host cells to combat difficult Methicillin-resistant Staphylococcus aureus (MRSA) infections. This breakthrough offers a promising treatment for intracellular MRSA and other pathogen infections.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Drug Delivery Systems
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health risk.
- Intracellular MRSA infections are challenging to treat with conventional antibiotics like vancomycin due to poor cellular uptake.
- Vancomycin's molecular properties limit its efficacy against pathogens residing within host cells.
Purpose of the Study:
- To develop a novel nanoparticle formulation for enhanced intracellular delivery of vancomycin.
- To overcome the limitations of vancomycin's cellular penetration for treating intracellular MRSA.
- To evaluate the efficacy of the developed nanoparticles against intracellular MRSA and other pathogens.
Main Methods:
- Formulation of vancomycin-loaded nanoparticles (PpZEV) using a blend of polymers: PLGA, PEG-PLGA, Eudragit E100, and a chitosan derivative (ZWC).
- Characterization of nanoparticle size (500-1000nm) and properties for preferential uptake by macrophages.
- Assessment of PpZEV nanoparticle antimicrobial activity against intracellular MRSA and other pathogens in vitro.
- Evaluation of PpZEV nanoparticle biodistribution in vivo after intravenous administration.
Main Results:
- PpZEV nanoparticles demonstrated preferential uptake by macrophages, facilitating intracellular vancomycin delivery.
- PpZEV nanoparticles exhibited superior antimicrobial activity against intracellular MRSA compared to free vancomycin.
- Intravenous administration of PpZEV nanoparticles led to rapid accumulation in the liver and spleen, key sites for intracellular infections.
- The formulation showed potential for treating intracellular MRSA and other intracellular pathogens.
Conclusions:
- PpZEV nanoparticles represent a promising drug delivery system for vancomycin to target intracellular MRSA infections.
- The developed nanoparticle formulation overcomes vancomycin's limitations in cellular uptake and intracellular pathogen eradication.
- PpZEV nanoparticles offer a potential therapeutic strategy for managing challenging intracellular bacterial infections.
