Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Gut-Restricted Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract (Caused by H. pylori and E. coli, etc.)

Version 1 : Received: 31 July 2023 / Approved: 1 August 2023 / Online: 2 August 2023 (08:39:27 CEST)

A peer-reviewed article of this Preprint also exists.

Zlotnikov, I.D.; Belogurova, N.G.; Poddubnaya, I.V.; Kudryashova, E.V. Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract. Pharmaceutics 2023, 15, 2353. Zlotnikov, I.D.; Belogurova, N.G.; Poddubnaya, I.V.; Kudryashova, E.V. Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract. Pharmaceutics 2023, 15, 2353.

Abstract

Helicobacter pylori, a gram-negative bacteria usually found in stomach and first part of small intestine, is known to cause infections and ulcers and may have association with cancer. Normally, the treatment options include combinations of antibiotics with proton pump inhibitors and antiinflammatory drugs. However, all of them have high systemic exposure, and hence, unfavourable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is very limited. We have attempted to develop a predominantly gut-restricted formulations of antibiotic + adjuvant combinations as a basis for potentially more safe and efficacious treatment of gastrointestinal tract infections. We have considered E. coli (as a model of H. pylori) and Lactobacilli to study the antibacterial activity of nanogel with combined drugs (classical antibiotics and individual components of essential oils). It has been shown that levofloxacin (LF) in combination with zephirol demonstrates synergy effect against E. coli (cell viability has decreased by about 50%) and weakens the effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant is also shown to be effective. Using FTIR and UV spectroscopy, it has been proved that chitosan nanogels with the drug are well adsorbed on the mucosal model, thereby increasing the bioavailability of drugs. Using ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which is potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. Thus, chitosan nanogels loaded with a combination of drugs can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract, and applicable to difficult-to-treat bacteria.

Keywords

gastrointestinal diseases; H. pylori model; chitosan nanogel; combined formulation adjuvant+antibiotic; antiadhesive agent

Subject

Biology and Life Sciences, Biology and Biotechnology

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