The Stomach Infections of the Stomach
Helicobacter pylori is an infection that occurs within the stomach and is interesting in terms of advanced drug delivery. H. pylori is a gram-negative, microaerophilic, spiral and flagellated bacterium, with a unipolar-sheathed flagella that provides motility. Its spiral shape and high motility allow it to penetrate mucus, resist gastric emptying and remain in the host gastric mucosa. Since its isolation in the early 1980s, it has now been firmly established that infection with this bacterium is the cause of chronic active gastritis and an aetiological factor in peptic ulcer disease, gastric mucosal-associated lymphoid tissue lymphoma and gastric carcinoma.
Although H. pylori is sensitive to many antibiotics in vitro, no single agent is effective alone in vivo and the treatment for eradication of H. pylori is complicated, requiring a minimum of two antibiotics in combination with gastric acid inhibitors. Helicobacter infections are currently treated with a first-line triple therapy treatment, consisting of a proton pump inhibitor and two antibiotics. None of the antibiotics used achieved sufficient eradication, therefore adjuvant therapy is required (35).
However, increasing resistance to current antibiotics is driving research to produce alternatives to the commonly used therapies. In addition to increasing levels of antibiotic resistance, the hostile environment of the stomach, reducing antibiotic bioavailability at the site of action, contributes to failures in treatment. The bacterium resides in the surface layers of the stomach (Fig. 3), both in the mucus and the mucosa. With conventional oral therapy, the majority of antibiotic present at the site of Helicobacter infection (the gastric mucus) must be exsorbed from the blood. Delivery of amoxicillin across the gastric mucosa is poor compared with other drugs such as metronidazole and clarithromycin (36,37). Instability of antibiotics such as
amoxicillin and clarithromycin in gastric acid may also contribute to the failure of such agents to completely eradicate the infection (38).
Major obstacles in the eradication of H. pylori are therefore the presence of antibiotic-resistant bacteria, a therapy requiring multiple drugs with complicated dosing schedules and bacterial residence in an environment where high drug concentrations are difficult to achieve. In order to ensure that the therapy is adequately delivered to the unique niche of the gastric mucosa, it will be necessary to employ a drug delivery system.
Continue reading here: Advanced Formulations Targeting the Stomach
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