Chronic intracellular infections caused by drug-resistant pathogens pose a challenge to the treatment of chronic osteomyelitis. Such treatment requires an intracellular delivery system for the sustained release of antibiotics such as vancomycin (VCM), which is an antibiotic of last resort used against many clinically resistant bacteria. In this work, we report VCM-loaded N-trimethyl chitosan (TMC) nanoparticles and their potential application for drug delivery. The results showed that the prepared nanoparticles were predominantly spherical in shape with an average particle diameter of 220 nm, a positive zeta potential, and a loading efficiency of 73.65%˘1.83%. Furthermore, their drug release profile followed the Higuchi model for sustained release, with non-Fickian diffusion. Over a 24-h period, 6.51%˘0.58% of the drug within the optimized nanoparticles was released. In vitro cytology showed that osteoblasts (OBs) exhibited higher alkaline phosphatase activity (ALP) after exposure to TMC nanoparticle material. Furthermore, TMC nanoparticles increased the uptake of water-soluble quantum dots (QDs) by OBs, and both nanoparticles and VCM/TMC mixtures improved OB proliferative activity. We also investigated the minimum inhibitory concentration (MIC, 60 µg/mL), half maximal inhibitory concentration (IC50, 48.47 µg/mL), diameter of inhibition zone (DIZ, 1.050 cm), Polymers 2015, 7 1851 and turbidimetric (TB) assay of nanoparticles. All data demonstrated that VCM/TMC nanoparticles had excellent antibacterial activity against the Gram-positive bacterium Staphylococcus aureus. These findings suggest that VCM-loaded TMC nanoparticles have good potential for the sustained delivery of antibiotics to bone infections.
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.
The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd.
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