Helicobacter infection is widespread and has been shown to be a major causative agent for gastric carcinoma. Current therapies involve combination therapy including antibiotics but since the bacterium resides in the gastric mucus, antibiotic presentation is inefficient. A vehicle for topical administration of antibiotics directly to the gastric mucus layer may provide an enhanced method for H. pylori eradication.
The specific aims outlined within this proposal are to develop thermoreversible gel formulations with characterized physico-chemical properties. Properties to be studies include temperature and time of gelation, viscosity of the liquid form, hydrophobicity, adhesivity, diffusivity of drugs from the gel matrix and the interactions of the gels with mucus. Two classes of formulations are to be evaluated: poloxamers containing different excipients and fluorocarbon-hydrocarbon diblocks containing medium chain triglycerides. Concentrations of excipients and gels will be varied to optimize drug delivery properties. Since poloxamers have a known safety profile, the degree of gelation, gelation temperature, and effect of excipients will be correlated with gastric emptying times in human volunteers as determined by scintography. The overall aim is to devise a short, effective and inexpensive treatment for human H. pylori infections by developing a gastric retentive formulation for topical antibiotic administration to the gastric mucus.
The potential commercial applications of this work are to provide improved drug formulations for the treatment of gastric mucosal diseases such as H. pylori infections, atrophic gastritis and gastric cancer. The overall aim to this end is to assess the potential of thermoreversible poloxamer-based gels for prolonged topical delivery of drugs to the stomach mucosal lining.
