Development, characterization and evaluation of antibacterial efficacy of actively targeted gold-polydopamine nanoparticle formulations for tuberculosis treatment.

Abstract

Tuberculosis (TB) is one of the oldest known diseases in the world and it remains a significant public health challenge. The increasing resistance of microorganisms to antibiotics underlines the necessity of appropriate use of antibiotics and correct dosage in treatment. In some cases, frequent and high-dose drug therapy is required, which can lead to serious organ damage in the liver and kidneys in long-term treatment. However, this problem can be overcome by using appropriate drug delivery systems that allow more effective treatments at lower doses. Here, we developed a drug delivery system specifically targeting tuberculosis using gold (Au)-polydopamine (PDA) nanoparticles and modified with polyethylene glycol (PEG), a targeting agent (antibody), and the antibiotic linezolid, resulting in Au-PDA-PEG-Antibody-Linezolid nanoparticles. We successfully developed and characterized these active targeted nanoparticles using UV-Vis absorbance spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta potential measurements, and surface-enhanced Raman spectroscopy (SERS) measurements. Additionally, the developed formulations were compared with the commercial product through in vitro release studies, and antibacterial efficacy studies were conducted on multidrug-resistant tuberculosis (MDR-TB) strains. The targeted drug delivery system might be able to reduce side effects by increasing treatment effectiveness at lower doses. Additionally, our study is the one of the first example to feature actively targeted nanoparticle formulations using the active ingredient linezolid and PEGs with different chemical structures.