Tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP): Rejuvenation of an obsolete antibiotic to further action

• Published in: Biochimica et biophysica acta Vol. 1860; no. 9; pp. 1929 - 1941
• Main Authors: Mukherjee, Riya, Patra, Mousumi, Dutta, Debanjan, Banik, Milon, Basu, Tarakdas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2016
• Subjects: agar; Animals; Anti-Bacterial Agents - pharmacology; antibacterial properties; bacteria; Bacteria - drug effects; Calcium phosphate nanoparticle; calcium phosphates; Calcium Phosphates - administration & dosage; Cell Membrane - drug effects; Cell Membrane - microbiology; cell membranes; Danio rerio; death; developing countries; dialysis; Diarrhea-causing multi-drug resistant bacteria; Drug Resistance, Multiple, Bacterial - drug effects; energy-dispersive X-ray analysis; Escherichia coli; fish larvae; flow cytometry; fluorescence emission spectroscopy; Fourier transform infrared spectroscopy; health services; infectious diseases; Larva - drug effects; Larva - microbiology; MIC; minimum inhibitory concentration; multiple drug resistance; nanoparticles; Nanoparticles - administration & dosage; Particle Size; Protein Synthesis Inhibitors - pharmacology; Rejuvenation - physiology; Salmonella; Shigella flexneri; Tetracycline; Tetracycline - pharmacology; toxicity; transmission electron microscopy; Zebra fish; Zebrafish - microbiology; Calcium phosphate nanoparticle; Diarrhea-causing multi-drug resistant bacteria; MIC; Zebra fish; Tetracycline
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.06.006

Increasing resistance in bacteria towards antibiotics has made it imperative to research on their revitalization to combat infectious diseases. This study dealt with synthesis of a nano-form of the antibiotic tetracycline, its characterization and potency of killing different multi-drug resistant diarrhea-causing bacteria. Nano-formulation was done by loading tetracycline within biocompatible calcium phosphate nanoparticle. The synthesized tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP) was characterized by the techniques like TEM, DLS, EDS, FTIR, spectrofluorimetry and dialysis. Bactericidal activity of nano-particulate tetracycline was investigated by agar plating, spectrophotometry, phase contrast-fluorescence-atomic force microscopy and flow cytometry techniques. The Tet-CPNPs were 8±5nm in size and nearly spherical in shape, efficiency of tetracycline loading in CPNP was about 20% and the release of antibiotic from Tet-CPNPs was sustainable during 7days. Minimum inhibitory concentration (MIC) of Tet-CPNP on multiple antibiotic (including tetracycline) resistant bacteria like Escherichia coli, Salmonella kentuckey and Shigella flexneri was in the range of 20–40μg/ml, whereas MIC of free tetracycline was in the range of 150–180μg/ml. NP-mediated cell filamentation and cell membrane disintegration caused cell killing. Moreover, death of Shigella-infected Zebra fish larvae was stalled by Tet-CPNP treatment. CPNP itself had no toxic effect on bacteria as well as on Zebra fish. Our nano-formulation of tetracycline might reclaim a nearly obsolete antibiotic to further potential function. Such a study on revival of an old, cheap, broad-spectrum antibiotic to further action is highly beneficial to developing countries with limited health care budgets. [Display omitted] •Reclamation of an old, obsolete antibiotic in new nano-form by a nanosized biocompatible carrier.•In vitro and in vivo results show it could kill resistant bacteria at a much lesser concentration than the free drug.•Loss of membrane integrity may be the cause of cellular killing in bacterial cell.•These particles exhibited sustained release of antibiotic for up to 7days.