Efficient induction of antimicrobial activity with vancomycin nanoparticle-loaded poly(trimethylene carbonate) localized drug delivery system

Yang Zhang,1,* Ruo-jia Liang,2,* Jiao-jiao Xu,3 Li-feng Shen,1 Jian-qing Gao,4 Xu-ping Wang,1 Na-ni Wang,1 Dan Shou,1 Ying Hu3 1Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, 2Department of Gynaecology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, 4College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Surgery and the local placement of an antibiotic are the predominant therapies to treat chronic osteomyelitis. Vancomycin-loaded N-trimethyl chitosan nanoparticles (VCM/TMC NPs) as a potential drug delivery system have high intracellular penetration and effective intracellular antibacterial activity. This study investigated the effects of a biocompatible material, poly(trimethylene carbonate) (PTMC), to increase the sustained effectiveness of an intracellular antibiotic and its potential application in antibiotic delivery. VCM/TMC NP-PTMC was characterized using scanning electron microscopy and Fourier transform infrared spectroscopy to determine the morphology, stability and chemical interaction of the drug with the polymer. Further, the biodegradation, antibacterial activity, protein adsorption, cell proliferation and drug release characteristics were evaluated. In addition, a Staphylococcus aureus-induced osteomyelitis rabbit model was used to investigate the antibiotic activity and bone repair capability of VCM/TMC NP-PTMC. The results showed that the composite beads of VCM/TMC NPs followed a sustained and slow release pattern and had excellent antibacterial activity and a higher protein adsorption and cell proliferation rate than the VCM-PTMC in vitro. Furthermore, VCM/TMC NP-PTMC inhibits bacteria and promotes bone repair in vivo. Thus, VCM/TMC NP-PTMC might be beneficial in periodontal management to reduce the bacterial load at the infection site and promote bone repair. Keywords: vancomycin-loaded N-trimethyl chitosan nanoparticles, poly(trimethylene carbonate), sustained release, intracellular antibiotic effect, bone infectio