Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages.
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.
School of Biotechnology, Campus-11, KIIT University, Bhubaneswar, Orissa-751024, India.
Rashmirekha
R
Pati
School of Applied Sciences, Campus-3, KIIT University, Bhubaneswar, Orissa-751024, India.
Rojalin
R
Sahu
School of Applied Sciences, Campus-3, KIIT University, Bhubaneswar, Orissa-751024, India.
Jagannath
J
Panda
School of Biotechnology, Campus-11, KIIT University, Bhubaneswar, Orissa-751024, India.
Avinash
A
Sonawane
D000072283:A549 Cells; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008856:Microscopy, Fluorescence; D009163:Mycobacterium bovis / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D045663:Quantum Dots / Q000737:chemistry*; D012293:Rifampin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012834:Silver / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014168:Transferrin / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D000995:Antitubercular Agents; D004337:Drug Carriers; D014168:Transferrin; D012834:Silver; D015032:Zinc; D012293:Rifampin