Evaluation of the clearance characteristics of bioadhesive systems in humans

Soane, R. J.; Frier, M.; Perkins, Alan C.; Jones, Nicholas S.; Davis, S.S.; Illum, Lisbeth

doi:10.1016/s0378-5173(98)00367-6

Cited by 326 publications

(146 citation statements)

References 23 publications

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“…The fact that only partial protection was observed in vivo using chitosan may be due to its short half-life 11 . Our results may contribute to understand why only small numbers of bacteria are sufficient to induce HUS in humans.…”

Section: Discussionmentioning

confidence: 99%

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

et al. 2014

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Shiga toxin (Stx) is considered the main virulence factor in Shiga toxin-producing Escherichia coli (STEC) infections. Previously we reported the expression of biologically active Stx by eukaryotic cells in vitro and in vivo following transfection with plasmids encoding Stx under control of the native bacterial promoter. Since stx genes are present in the genome of lysogenic bacteriophages, here we evaluated the relevance of bacteriophages during STEC infection. We used the non-pathogenic E. coli K12 strain carrying a lysogenic 933W mutant bacteriophage in which the stx operon was replaced by a gene encoding the green fluorescent protein (GFP). Tracking GFP expression using an In Vivo Imaging System (IVIS), we detected fluorescence in liver, kidney, and intestine of mice infected with the recombinant E. coli strain after treatment with ciprofloxacin, which induces the lytic replication and release of bacteriophages.In addition, we showed that chitosan, a linear polysaccharide composed of D-glucosamine residues and with a number of commercial and biomedical uses, had strong anti-bacteriophage effects, as demonstrated in vitro and in vivo. These findings bring promising perspectives for the prevention and treatment of hemolytic uremic syndrome (HUS) cases.

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Section: Discussionmentioning

confidence: 99%

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

et al. 2014

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“…In solution, chitosan is positively charged and binds strongly to negatively charged materials such as cell surfaces and mucus, thereby enabling increased antigen‐retention time in the nasal cavity. A g‐scintigraphy technique has demonstrated chitosan’s behaviour as a bioadhesive material in the nasal cavity 33 . The absorption‐promoting effect of chitosan is also enhanced by modification of the paracellular transport system as demonstrated by investigations in cell culture as well as in animal models 34 .…”

Section: Discussionmentioning

confidence: 99%

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Svindland

Jul-Larsen

Pathirana

et al. 2011

Influenza Resp Viruses

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Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose‐sparing strategies and an efficient mass‐vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose‐sparing potential of a chitosan‐adjuvanted intranasal H5N1 (RG‐14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)‐adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non‐adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG‐14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan‐adjuvanted SU vaccine induced an immune response superior to that of the non‐adjuvanted SU vaccine. Compared with the non‐adjuvanted SU group, the chitosan‐adjuvanted SU vaccine elicited higher numbers of influenza‐specific antibody‐secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T‐helper 1/T‐helper 2 cytokine response in the chitosan‐adjuvanted SU groups, and these groups had an increased percentage of virus‐specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non‐adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan‐adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T‐helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross‐clade serum reactivity, improved B‐ and T‐cell responses and dose‐sparing potential of chitosan show that a chitosan‐adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

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“…Enhancing mechanisms include decrease in mucociliary clearance, reduction of mucus viscosity or elasticity, inhibition of enzyme activity, opening of tight junctions, and solubilization or stabilization of the drug molecule [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Mucociliary clearance can be defined as combined actions of the mucus layer and the cilia, which is an important factor in the physiological defence of the respiratory tract against inhaled hazardous particles [13].…”

Section: Limitations Of Nasal Deliverymentioning

confidence: 99%