Development of a Nanodiamond-Based Antibiotic Carrier for Killing Multidrug-Resistant Bacteria

碩士 === 國立暨南國際大學 === 應用化學系 === 106 === The emergence of multidrug-resistant (MDR) bacteria has become one of the most pressing issues that threaten the health of human. Nanoparticle-assisted drug delivery has shown great promise for treating MDR. Recently, interest in using nanoparticle-based approac...

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Bibliographic Details
Main Authors: LO, YU-CHI, 羅宇琪
Other Authors: WU, CHIH-CHE
Format: Others
Language:zh-TW
Published: 2018
Online Access:http://ndltd.ncl.edu.tw/handle/r429k8
Description
Summary:碩士 === 國立暨南國際大學 === 應用化學系 === 106 === The emergence of multidrug-resistant (MDR) bacteria has become one of the most pressing issues that threaten the health of human. Nanoparticle-assisted drug delivery has shown great promise for treating MDR. Recently, interest in using nanoparticle-based approaches to combat difficult infections has rapidly grown due to the many advantages offered over conventional treatment with free antibiotics. Nanodiamond (ND) is a promising biomedical material for drug delivery due to their excellent physiological properties including high biocompatibility, narrow size distribution, high surface area-to-volume ratio, and facile surface functionalization for drug loading. NDs have shown the ability to overcome drug efflux in several multidrug-resistance (MDR) cancer cell lines and shown increased apoptosis in liver and mammary tumors in vivo. Here, ND is immobilized with ciprofloxacin (CFX) to form a ND-CFX nanodrug for combating MDR bacteria. The composites were prepared by adsorption ciprofloxacin on the surface of nanodrug. Results showed that ND-CFX not only achieve 1.84% loading capacity and biocompatibility, but also sustainable releases CFX in a pH-dependent manner over 5 days. Compared to free CFX drug, ND-CFX can more effectively inhibit the growth of MDR E. coli., leading to a lower specific growth constant. Matrix-assisted Laser Desorption /Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) analysis of bacteria lysates confirmed that ND-CFX is a more effective bactericidal drug than free CFX. 4 μg/mL of ND-CFX can kill 91.5% of MDR E. coli cells in a culture with a density of 105 CFU/mL in 2 h. The improved bactericidal performance was attributed to the effective ND-assisted drug delivery, which bypasses multidrug efflux pumps and improve therapeutic efficacy. NDs with excellent physiological properties can serve as an excellent nanocarrier for drug delivery in the treatment of MDR E. coli. These results show that the NDs can serve as an effective antibiotic carrier in the MDR E. coli. It can be potentially useful for clinical treatment of antibiotic-resistant bacterial infections.