Delivery of antimicrobial protein into biofilm using hollow mesoporous silica nanoparticles

Objectives: Bacterial biofilms related infections are very challenging as bacteria survive in the presence of high concentration of antibiotics, which leads to treatment failure and infections recurrence. The aim of this study is to use novel hollow mesoporous silica nanoparticles (MSNs) as a drug delivery system to enhance the antibacterial activity of lysozyme, a natural antimicrobial protein, against Escherichia coli (E. coli) biofilm.
Methods: Hollow mesoporous silica nanoparticles with large pores (HMSN-LP) were synthesized using an oil-water system. The loading and release behavior of lysozyme into MSNs were evaluated. The antimicrobial activity of lysozyme loaded HMSN-LP towards E. coli biofilm was also tested using LIVE/DEAD staining and spread plate method compared to MSNs with smaller pores and free lysozyme.
Results: The novel hollow MSNs with large cone-shaped pores has been successful synthesized and the large pores enable the high lysozyme loading capacity and a sustained release behavior. The penetration test showed MSNs can deliver their payload into biofilms effectively. The enhanced antibacterial effect of lysozyme loaded HMSN-LP on E.coli biofilm was also demonstrated.
Conclusions: We report the delivery of antimicrobial protein into biofilm using MSNs for the first time. With rational design, MSNs with large pores are successfully synthesized and demonstrated high therapeutic activity toward E. coli biofilms. Our design may be developed as novel carriers for antibacterial drugs/proteins/combinations against infectious pathogens.