title: Design and evaluation of novel pH-sensitive ureido-conjugated chitosan/TPP nanoparticles targeted to Helicobacter pylori.
abstract: The covalently modified ureido-conjugated chitosan/TPP multifunctional nanoparticles have been developed as targeted nanomedicine delivery system for eradication of Helicobacter pylori. H. pylori can specifically express the urea transport protein on its membrane to transport urea into cytoplasm for urease to produce ammonia, which protects the bacterium in the acid milieu of stomach. The clinical applicability of topical antimicrobial agent is needed to eradicate H. pylori in the infected fundal area. In this study, we designed and synthesized two ureido-conjugated chitosan derivatives UCCs-1 and UCCs-2 for preparation of multifunctional nanoparticles. The process was optimized in order to prepare UCCs/TPP nanoparticles for encapsulation of amoxicillin. The results showed that the amoxicillin-UCCs/TPP nanoparticles exhibited favorable pH-sensitive characteristics, which could procrastinate the release of amoxicillin at gastric acids and enable the drug to deliver and target to H. pylori at its survival region effectively. Compared with unmodified amoxicillin-chitosan/TPP nanoparticles, a more specific and effective H. pylori growth inhibition was observed for amoxicillin-UCCs/TPP nanoparticles. Drug uptake analysis tested by flow cytometry and confocal laser scanning microscopy verified that the uptake of FITC-UCCs-2/TPP nanoparticles was associated with urea transport protein on the membrane of H. pylori and reduced with the addition of urea as competitive transport substrate. These findings suggest that the multifunctional amoxicillin-loaded nanoparticles have great potential for effective therapy of H. pylori infection. They may also serve as pharmacologically effective nanocarriers for oral targeted delivery of other therapeutic drugs to treat H. pylori.
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Zi-Wei
authors: ZW
authors: Jing
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Yi-Yang
authors: YY
authors: Jia
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Ning
authors: N
authors: Wan
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Min
authors: M
authors: Luo
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Meng-Lei
authors: ML
authors: Huan
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Tai-Bin
authors: TB
authors: Kang
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Si-Yuan
authors: SY
authors: Zhou
authors: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: blezhang@fmmu.edu.cn.
authors: Bang-Le
authors: BL
authors: Zhang
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D005434:Flow Cytometry; D057809:HEK293 Cells; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D011122:Polyphosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D014508:Urea / Q000737:chemistry* / Q000633:toxicity
chemical_list: D011122:Polyphosphates; D000658:Amoxicillin; D014508:Urea; D048271:Chitosan; C005692:triphosphoric acid
keywords: Chitosan; Helicobacter pylori; Multifunctional nanoparticles; Targeted delivery; pH-sensitive