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Formulation and evaluation of amoxicillin-loaded nanoemulsions using for Helicobacter pylori eradication

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Formulation and Evaluation of Amoxicillin-Loaded Nanoemulsions Using for Helicobacter pylori Eradication

1

Yu-Hsin Lin, 1Shih-Chang Tsai, 2Chih-Ho Lai, 3Chih-Wei Chou

1

Department of Biological Science and Technology, China Medical University

2

Department of Microbiology, School of Medicine, China Medical University

3

Department of Cosmeceutics, China Medical University

1

China Medical University, Taichung 40402, Taiwan

1

Phone:886-4-2205-3366; Fax:886-4-2207-1507; E-mail:ylhsin@mail.cmu.edu.tw Introduction

For effective H. pylori eradication, the standard treatment in the case is a combination of drugs, including antibiotics and a proton pump inhibitor1). The failure of antibiotic therapies could be attributable to the poor stability in the gastric acid, and the poor permeation of antibiotic across the mucus layer, where sufficient drug must diffuse to the bacteria2). We prepared nanoemulsion particles could encapsulate amoxicillin and infiltrate into the mucus layer, subsequently, amoxicillin release from amoxicillin-loaded nanoemulsion particles, then directly acts locally on H. pylori at a bactericidal concentration (Figure 1a). We investigated amoxicillin release characteristics from the nanoemulsion particles and examined the inhibition of H. pylori growth. The effect of the nanoemulsion particles and their mechanism of interaction with H. pylori were investigated in the human gastric adenocarcinoma cell line with confocal laser scanning microscopy. We also assessed the in vivo clearance effect of amoxicillin-loaded chitosan/heparin nanoemulsion particles in H. pylori infected mice.

Results and Discussion

H. pylori colonizes the human gastric mucus layer and adheres to surface epithelial cells, it produces a vacuolating cytotoxin with the ability to modulate the integrity of the epithelium. H. pylori may preferentially adhere not only to the gastric epithelium surface, but also close to the tight junctions of gastric mucous cells3). The ideal antibiotic dose for H. pylori eradication must not only localize in the stomach, but must also interact locally with the bacterium.

In our study of the relationship between

amoxicillin-loaded chitosan/heparin nanoemulsion particles and H. pylori (Figure

1b), we used CLSM to show that prepared fluorescent FA-amoxicillin loaded in Cy3-chitosan/heparin nanoemulsion particles (Cy3-chitosan: red spot, FA-amoxicillin: green spot) co-localized and interacted locally at sites of H. pylori infection. To improve the efficacy of anti-H. pylori agents, antibiotics need to localize at the H. pylori infection site in the gastric epithelium. As shown Campylobacter-like organism test in Figure 1c, the clearance of H. pylori in vivo was observed with doses amoxicillin in

amoxicillin–loaded chitosan/heparin nanoemulsion particles; the clearance rate

showed a more complete H. pylori clearance effect than with amoxicillin alone.

Reference

1) van der Hulst, RW. et al. Helicobacter. 1996, 1, 6.

Figure 1. (a)A representation for particles for eradicating H. pylori. (b)Fluorescent images of AGS cell infected with fluorescent H. pylori and nanoemulsion particles. (c)Effects of amoxicillin-nanoemulsion particles in H. pylori-induced gastric infection mouse model. 2) Endo, H. et al. J Antimicr. Chem. 2001, 48, 923. 3) Patel, JK. et al. Curr. Drug. Deliv. 2007, 4, 41.

數據

Figure 1. (a)A representation for particles for  eradicating  H. pylori. (b)Fluorescent images of  AGS cell infected with fluorescent H

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