Zlotnikov Igor D, Belogurova Natalya G, Poddubnaya Irina V, Kudryashova Elena V
Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, 119991 Moscow, Russia.
Research Laboratory of Aquatic Environment Protection and Ichthyopathology, Saratov State University of Genetics, Biotechnology and Engineering Named after N.I. Vavilov, 410005 Saratov, Russia.
Pharmaceutics. 2023 Sep 20;15(9):2353. doi: 10.3390/pharmaceutics15092353.
Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited. Chitosan and nanogels based on chitosan presumably are not absorbed from the gastrointestinal tract and are known to adhere to the mucus. Therefore, they can serve as a basis for the local delivery of antibacterial drugs, increasing their exposure at the predominant location of therapeutic targets, thus improving the risk/benefit ratio. We have used ATCC 25922 (as a screening model of pathogenic bacteria) and (as a model of a normal microbiome) to study the antibacterial activity of antibacterial drugs entrapped in a chitosan nanogel. Classical antibiotics were studied in a monotherapeutic regimen as well as in combination with individual terpenoids and flavonoids as adjuvants. It has been shown that levofloxacin (LF) in combination with zephirol demonstrate synergistic effects against (cell viability decreased by about 50%) and, surprisingly, a much weaker effect against . A number of other combinations of antibiotic + adjuvant were also shown to be effective. Using FTIR and UV spectroscopy, it has been confirmed that chitosan nanogels with the drug are well adsorbed on the mucosal model, providing prolonged release at the target location. Using an ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which are potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. In vivo experiments (on sturgeon fish) showed the effective action of antibacterial formulations developed based on LF in chitosan nanogels for up to 11 days. Thus, chitosan nanogels loaded with a combination of drugs and adjuvants can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract.
细菌感染通常与各种病理状况相关，出现在胃部和小肠的起始部分，这些病理状况包括溃疡、炎症性疾病，有时还与癌症有关。治疗方案可能包括抗生素与质子泵抑制剂及抗炎药物的联合使用。然而，所有这些药物都有较高的全身暴露量，因此会产生不良副作用，而它们在细菌主要存在部位——胃黏液中的暴露量却很有限。壳聚糖以及基于壳聚糖的纳米凝胶大概不会从胃肠道吸收，并且已知它们会附着在黏液上。因此，它们可作为局部递送抗菌药物的基础，增加药物在治疗靶点主要存在部位的暴露量，从而改善风险/效益比。我们使用了ATCC 25922（作为病原菌的筛选模型）和（作为正常微生物群的模型）来研究包裹在壳聚糖纳米凝胶中的抗菌药物的抗菌活性。经典抗生素在单一治疗方案中以及与作为佐剂的个别萜类化合物和黄酮类化合物联合使用时都进行了研究。结果表明，左氧氟沙星（LF）与洗必泰联合使用对（细胞活力下降约50%）显示出协同作用，令人惊讶的是，对的作用要弱得多。还显示出许多其他抗生素+佐剂的组合也是有效的。使用傅里叶变换红外光谱（FTIR）和紫外光谱，已证实含有药物的壳聚糖纳米凝胶能很好地吸附在黏膜模型上，在靶点部位实现缓释。使用ABTS测定法，显示出黄酮类化合物和其他药物的抗氧化特性，这对于将病原体产生的毒素和自由基的有害影响降至最低可能是必要的。体内实验（在鲟鱼身上）表明，基于LF的壳聚糖纳米凝胶抗菌制剂能有效作用长达11天。因此，负载药物和佐剂组合的壳聚糖纳米凝胶可被视为治疗胃肠道传染病的一种新策略。
