rifampin and nile-red

Dormant, slow-growing, antibiotic-tolerant Mycobacterium tuberculosis undermine the shortening of tuberculosis treatment to less than 6 months and are thought to be characterised by intracellular lipid bodies. Antibiotic effects on such persisting bacilli escape evaluation as they cannot be readily cultured. We identified cells containing lipid bodies in sputum smears from 86 newly diagnosed pulmonary tuberculosis patients and monitored these cells daily in 42 patients over the first 14 days of treatment with rifampicin, the experimental compound SQ-109, or both agents combined. Counts of Nile-Red-positive lipid-body containing cells were correlated with those of Auramine-O-positive cells and colony forming units of viable Mycobacterium tuberculosis on agar plates. Rifampicin but not SQ-109 significantly reduced colony forming units but all treatments distinctively and significantly changed the proportions of lipid body-containing bacilli and viable Mycobacterium tuberculosis. Monitoring lipid-body containing bacilli in sputum during treatment with experimental antituberculosis regimens may identify putative treatment-shortening regimens.

Topics: Adamantane; Antitubercular Agents; Bacterial Load; Benzophenoneidum; Colony Count, Microbial; Drug Monitoring; Drug Therapy, Combination; Ethylenediamines; Fluorescent Dyes; Humans; Lipid Droplets; Microscopy, Fluorescence; Mycobacterium tuberculosis; Oxazines; Predictive Value of Tests; Rifampin; South Africa; Sputum; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary

One of the most effective strategies to enhance the bioavailability and the therapeutic effect of hydrophobic drugs is the use of nanocarriers. We have used κ-carrageenan extracted from Kappaphycus alvarezii to produce oligocarrageenan via an enzymatic degradation process. Polycaprolactone (PCL) chains were grafted onto the oligocarrageenans using a protection/deprotection technique yielding polycaprolactone-grafted oligocarrageenan. The resulting amphiphilic copolymers formed spherical nanomicelles with a mean size of 187 ± 21 nm. Hydrophobic drugs such as curcumin were efficiently encapsulated in the micelles and released within 24-72 h in solution. The micelles were non-cytotoxic and facilitated the uptake of curcumin by endothelial EA-hy926 cells. They also increased the anti-inflammatory effect of curcumin in TNF-alpha-induced inflammation experiments. Finally, in vivo experiments supported a lack of toxicity in zebrafish and thus the potential use of polycaprolactone-grafted oligocarrageenan to improve the delivery of hydrophobic compounds to different organs, including liver, lung and brain as shown in mice.

Topics: Acetylation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cell Line; Curcumin; Drug Carriers; Drug Liberation; Female; Gammaproteobacteria; Glycoside Hydrolases; Humans; Hydrolysis; Male; Mice, Inbred C57BL; Micelles; Oligosaccharides; Oxazines; Particle Size; Polyesters; Rhodophyta; Rifampin; Zebrafish

The aim of this work is to monitor the changes in microstructure in nonionic Brij 96 microemulsions and to locate the solubilization loci of antituberculosis drugs (of variable solubility using photophysical and thermoanalytical properties. Using properties such as spectral shift, Stroke's shift, and anisotropy for two dyes, that is, Nile red (NR) and tris(2,2'-bipyridine)ruthenium(II) dichloride (RC), the structure of microemulsions has been investigated. With the help of spectral and deconvoluted analysis, it has been seen that rifampicin (RIF) shows a strong interaction with NR and isoniazid (INH) and pyrazinamide (PZA) with RC. It has been concluded that RIF molecules are mainly present at the interface toward oil side and INH toward hydrophilic side, whereas PZA remains in free water. The findings have been correlated with aqueous solubility drugs and partition coefficients. Differential scanning calorimetry elucidates the state of water in microheterogeneous environment and variation of different states, that is, free, bound, interphasal, and nonfreezable water with dilution. In addition, it confirmed the stability and location of the drugs in the prepared Brij 96 microemulsion formulations. A good agreement between both the studies has been achieved. These findings will help in elucidating the drug delivery properties of anti-TB drugs-loaded microemulsion formulations in future.

Topics: 2,2'-Dipyridyl; Antitubercular Agents; Calorimetry, Differential Scanning; Coordination Complexes; Drug Carriers; Drug Compounding; Drug Stability; Emulsions; Fluorescence Polarization; Fluorescent Dyes; Hydrophobic and Hydrophilic Interactions; Isoniazid; Models, Chemical; Oxazines; Plant Oils; Polyethylene Glycols; Pyrazinamide; Rifampin; Solubility; Spectrometry, Fluorescence; Water