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Ureido-modified carboxymethyl chitosan-graft-stearic acid polymeric nano-micelles as a targeted delivering carrier of clarithromycin for Helicobacter pylori: Preparation and in vitro evaluation

Cong, Ying, Geng, Jiayue, Wang, Hongying, Su, Jing, Arif, Muhammad, Dong, Quanjiang, Chi, Zhe, Liu, Chenguang
International journal of biological macromolecules 2019 v.129 pp. 686-692
Helicobacter pylori, bioavailability, chitosan, clarithromycin, composite polymers, cytotoxicity, drugs, gastric juice, in vitro studies, mucus, particle size, stearic acid, stomach, urea
The effect of antibiotics in the stomach for curing Helicobacter pylori infection is hampered by the adverse gastric environment and low bioavailability of the administered drugs. Concerning these challenges, a polymeric nano-micelle was developed. Initially, carboxymethyl chitosan (CMCS) was hydrophobically modified with stearic acid (SA), and the obtained CMCS-g-SA co-polymers was further conjugated with urea to acquire U-CMCS-g-SA co-polymers. Sphere-shaped nano-micelles (UCS-NMs) with the particle sizes of approximately 200nm were obtained with the U-CMCS-g-SA co-polymers. It was specified that this nano-micelle had no cell toxicity to AGS cells, and it could maintain a stable particle size for 6h in simulated gastric fluid and for 24h in 1×PBS. Attractively, the CMCS backbones granted this nano-micelle an excellent retention time in the stomach, almost 24h; meanwhile, the grafted ureido groups conferred effective targeting to H. pylori. This nano-micelle could load clarithromycin with high efficiency and exhibited slow release of this antibiotic in a slightly alkaline environment. In vitro inhibitory assay also indicated that a significantly enhanced anti-H. pylori activity was achieved by using this nano-micelle. This work demonstrated that the U-CMCS-g-SA nano-micelle is a proper carrier for targeted delivery of clarithromycin to H. pylori under the gastric mucus layer.