Chitosan nanofibrous scaffold with graded and controlled release of ciprofloxacin and BMP-2 nanoparticles for the conception of bone regeneration.

The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.

Lipid-Coated Hybrid Nanoparticles for Enhanced Bacterial Biofilm Penetration and Antibiofilm Efficacy.

Up to 80% of all infections are biofilm-mediated and they are often challenging to treat as the underlying bacterial cells can become 100- to 1000-fold more tolerant toward antibiotics. Antibiotic-loaded nanoparticles have gained traction as a potential drug delivery system to treat biofilm infections. In particular, lipid-coated hybrid nanoparticles (LCHNPs) were investigated on their capability to deliver antibiotics into biofilms. In this study, LCHNPs composed of a poly(lactic-co-glycolic acid) (PLGA) core and dioleoyl-3-trimethylammonium propane (DOTAP) lipid shell were developed and loaded with vancomycin (Van). In vitro antibacterial and antibiofilm tests were performed to evaluate the antimicrobial efficacy of the LCHNPs. LCHNPs were successfully fabricated with high vancomycin encapsulation and loading efficiencies, and exhibited enhanced antibacterial effects against planktonic Staphylococcus aureus USA300 when compared against Free-Van and Van-PLGANPs. When used to treat USA300 biofilms, Van-LCHNPs eradicated up to 99.99% of the underlying biofilm cells, an effect which was not observed for Free-Van and Van-PLGANPs. Finally, we showed that by possessing a robust DOTAP shell, LCHNPs were able to penetrate deeply into the biofilms.

Therapeutic lipid-coated hybrid nanoparticles against bacterial infections.

One of the most important health concerns in society is the development of pathogen-causing nosocomial infections. Since the first discovery of antibiotics, bacterial infections have been highly treatable. However, with evolution and the nondiscretionary usage of antibiotics, pathogens have also found new ways to survive the onslaught of antibiotics by surviving intracellularly or through the formation of obstinate biofilms, and through these, the outcomes of regular antibiotic treatments may now be unsatisfactory. Lipid-coated hybrid nanoparticles (LCHNPs) are the next-generation core-shell structured nanodelivery system, where an inorganic or organic core, loaded with antimicrobials, is enveloped by lipid layers. This core-shell structure, with multifarious decorations, not only improves the loading capabilities of therapeutics but also has the potential to improve therapeutic delivery, especially for targeting biofilm-based and intracellular bacterial infections. Although there has been significant interest in the development of LCHNPs, they have yet to be widely exploited for bacterial infections. In this review, we will provide an overview on the latest development of LCHNPs and the various approaches in synthesizing this nano-delivery system. In addition, a discussion on future perspectives of LCHNPs, in combination with other novel anti-bacterial technologies, will be provided towards the end of this review.