Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages

• Published in: Scientific reports Vol. 6; no. 1; p. 24184
• Main Authors: Pati, Rashmirekha, Sahu, Rojalin, Panda, Jagannath, Sonawane, Avinash
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-04-2016; Nature Publishing Group
• Subjects: 14/19; 140/131; 140/146; 631/326; 64/60; 692/699/255/1856; 96/106; A549 Cells; Animals; Antibacterial activity; Antitubercular Agents - chemistry; Antitubercular Agents - metabolism; Antitubercular Agents - pharmacology; Bacillus Calmette-Guerin vaccine; BCG; Cell Survival - drug effects; Chemotherapy; Cytotoxicity; Dendritic cells; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Encapsulation; Endocytosis; Epithelial cells; Genotoxicity; Humanities and Social Sciences; Humans; Immunofluorescence; Infrared spectroscopy; Luminescence; Macrophages; Macrophages - cytology; Macrophages - metabolism; Macrophages - microbiology; Magnetic Resonance Spectroscopy; Mice; Microscopy, Fluorescence; multidisciplinary; Mycobacterium bovis - drug effects; Mycobacterium smegmatis - drug effects; NMR; Nuclear magnetic resonance; Particle Size; Photoelectron Spectroscopy; Photons; Quantum Dots - chemistry; Rifampin; Rifampin - chemistry; Rifampin - metabolism; Rifampin - pharmacology; Science; Silver; Silver - chemistry; Spectroscopy, Fourier Transform Infrared; Transferrin - chemistry; Transferrins; Tuberculosis; Zinc; Zinc - chemistry
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24184

In order to improve the chemotherapy of tuberculosis, there is an urgent need to enhance the efficacy of existing agents and also to develop more efficient drug delivery systems. Here, we synthesized a novel anti-TB drug complex consisting of zinc and rifampicin (Zn-RIF) and encapsulated it into transferrin-conjugated silver quantum-dots (Zn-RIF-Tf-QD) to improve delivery in macrophages. Successful synthesis of Zn-RIF and Zn-RIF-Tf-QD was confirmed by UV/Vis-spectroscopy, TEM, FTIR, photoluminescence, XRD, XPS and NMR. The sizes of silver QDs and transferrin-conjugated QDs were found to be in the range of 5–20 nm. Activity assays showed that Zn-RIF-Tf-QD exhibited 10-fold higher antibacterial activity against
Mycobacterium smegmatis
and
Mycobacterium bovis
-BCG as compared to Zn-RIF, RIF and Zn. Immunofluorescence studies showed that Zn-RIF-Tf-QD-conjugates were actively endocytosed by macrophages and dendritic cells, but not by lung epithelial cells. Treatment with Zn-RIF-Tf-QD efficiently killed mycobacteria residing inside macrophages without exhibiting cytotoxicity and genotoxicity. Moreover, the conjugates remained stable for upto 48 h, were taken up into the late endosomal compartment of macrophages and released the drug in a sustainable manner. Our data demonstrate that Zn-RIF-Tf-QDs have a great potential as anti-TB drugs. In addition, transferrin-conjugated QDs may constitute an effective drug delivery system for tuberculosis therapy.