nystatin-a1 and triphosphoric-acid

Oral mucositis is a frequent and potentially severe complication of radiation or chemotherapy for cancer. Associated with atrophy and ulceration of the oral mucosa is an increased risk of infection, and the most common pathogenic agent is Candida. Chitosan is an excellent candidate for the treatment of oral mucositis. Its bioadhesive and antimicrobial properties offer the palliative effects of an occlusive dressing and the potential for delivering drugs, including anti-candidal agents. The aim of this study was to develop an occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis. Gel and film formulations were prepared using chitosans at different molecular weights and in different solvents. Nystatin, which is considered as a prophylactic agent for oral mucositis was incorporated into the formulations. The in vitro release of nystatin from the formulations was decreased with the increasing molecular weight of chitosan. The effect of the formulations was investigated in vivo in hamsters with chemotherapy-induced mucositis. Mucositis scores in groups treated with nystatin incorporated into gel and suspension formulations were significantly lower (p < 0.05) than those treated with the chitosan gel alone. Survival of animals in the treated groups was higher than that in the control group. The retention time and distribution of the gels in the oral cavity were investigated in healthy volunteers. A faster distribution of nystatin in the oral cavity was obtained using the suspension compared to the gels, but the nystatin saliva level decreased rapidly as well. A drug concentration above the minimum inhibitory concentration (MIC) value for Candida albicans (0.14 microg/ml) was maintained for longer periods of time at the application site (90 min) than at the contralateral site (45 min) in the oral cavity.

Topics: Adult; Animals; Antifungal Agents; Biological Availability; Body Weight; Chitosan; Cricetinae; Cross-Over Studies; Drug Delivery Systems; Drug Therapy, Combination; Fluorouracil; Gels; Histocytochemistry; Humans; Lactic Acid; Male; Mesocricetus; Mouth Mucosa; Nystatin; Polyphosphates; Saliva; Stomatitis; Survival Rate; Treatment Outcome; Water

The present study evaluated the use of nuclear magnetic resonance (NMR) spectroscopy to monitor directly and continuously intracellular sodium levels in rabbit renal cortical tubule suspensions. When the paramagnetic shift reagent dysprosium tripolyphosphate was added to the extracellular medium it was possible to resolve signals from intracellular and extracellular sodium without adversely affecting cellular viability. An efflux of intracellular sodium against a significant concentration gradient was observed when sodium-loaded cells were warmed from 4 to 37 degrees C. At 37 degrees C in steady state, inhibition of Na+-K+-ATPase activity by ouabain increased intracellular sodium content in a dose-dependent and time-dependent manner. A biphasic time course of increased intracellular sodium following ouabain (10(-3) M) suggested that the sodium permeability of the plasma membrane may decrease following pump inhibition, thus limiting sodium influx. Nystatin, an agent known to facilitate sodium entry across cell membranes, increased intracellular sodium fivefold. In another series of experiments several maneuvers were performed to ascertain the fraction of intracellular sodium that was NMR visible. Quantitative assessment of either an efflux or influx of sodium indicated that the NMR visibility of the transported sodium was 100%. Furthermore, disruption of the cell membranes with Triton X-100 showed that the entire pool of intracellular sodium was 100% NMR visible.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biological Transport, Active; Cell Membrane Permeability; Detergents; Dysprosium; Ion Channels; Kidney Tubules, Proximal; Magnetic Resonance Spectroscopy; Nystatin; Octoxynol; Ouabain; Polyethylene Glycols; Polyphosphates; Rabbits; Sodium; Sodium Isotopes; Spectrum Analysis