Effect of chitosan on epithelial permeability and structure

Dodane, V.; Khan, Mohammed Fahad; Merwin, June R.

doi:10.1016/s0378-5173(99)00030-7

Cited by 494 publications

(227 citation statements)

References 16 publications

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“…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 . Immunohistological studies have shown that chitosan can open the tight junctions between cells through an effect upon F‐actin filaments 35 .…”

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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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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“…The ability of biodegradable polymers to facilitate uptake and expression of nanoparticle-associated DNA plasmid by antigen-presenting cells has attracted attention, 34,35 and work in our laboratories 22,26 presented here and found in preclinical data from our previous study continues to yield promising results for polymer-based formulations. 25 In this study, after 49 days, we observed a significant increase of active GLP-1 in the plasma of animals injected s.c. (Figure 2a).…”

Section: Delivery Of Glp-1 Through Sc Injections Of Tncs Resulting mentioning

confidence: 73%

Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes

et al. 2011

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Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates blood glucose level post-prandially. It has been proposed that GLP-1 can be used in type 2 diabetes (T2D) mellitus treatment because of its insulinotropic action. Despite its remarkable advantages, GLP-1 suffers the disadvantage of an extremely short half-life owing to its degradation by the dipeptidyl peptidase IV protease. One way of overcoming this drawback is GLP-1 gene delivery. Here we show effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes (TNCs) in Zucker diabetic fatty (ZDF) animal model of T2D. The expression plasmid fused the GLP-1 gene to a Furin cleavage site was driven by a cytomegalovirus promoter/enhancer. TNCs were prepared by mixing this plasmid with chitosans of specific molecular weight (MW), degree of deacetylation (DDA) and ratio of chitosan amine to DNA phosphate (N:P ratio). Animals injected with the TNC chitosan 92-10-5 (DDA-MW-N:P) showed GLP-1 plasma levels of about fivefold higher than that in non-treated animals and the insulinotropic effect of recombinant GLP-1 was shown by a threefold increase in plasma insulin concentration when compared with untreated animals. Intraperitoneal glucose tolerance tests revealed an efficacious decrease of blood glucose compared with controls for up to 24 days after treatment, where injections of this formulation allowed near-normalization of blood glucose level. TNCs composed of specific chitosans and GLP-1-expressing plasmid constructs showed an impressive ability to harness the profound therapeutic potential of GLP-1 for the treatment of T2D mellitus.

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“…27) Although the enhancing effect of CH on the mucosal membranes is well established, there is no literature available for the CH skin penetration enhancing effect. In the case of using CH gel paracelular transport mechanism may be added to the transport of BRC through skin and a combined mechanism/effect could be effective.…”

Section: Resultsmentioning

confidence: 99%

Transdermal Administration of Bromocriptine.

Değim

Acartürk

Erdoğan

et al. 2003

Biological & Pharmaceutical Bulletin

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Bromocriptine (BRC) is a semi-synthetic ergot alkaloid and it has been used for the treatment of diseases caused by hyperprolactinemia and for some neurological disorders as a dopamine agonist in clinics.1) BRC is mainly used for the inhibition of lactation, 2) treatment of menstrual disorders, 3) Parkinson disease, 4) breast tumours, 5) infertility 6) and brain tumours. 7)Bromocriptine is well absorbed through the GI tract but it has low bioavailability because of the hepatic first pass effect, but many patients have complained with GI side effects, headache and dizziness.4) The long acting injectable form of BRC has been developed 2) and it avoids the gastrointestinal side effects but it is expensive and cannot be self-administered.An alternative delivery route such as vaginal application of BRC has been reported. 8,9) Bromocriptine is well absorbed from vagina. Acartürk and Altug have studied the vaginal ring formulation of BRC with polydimethylsiloxane in vitro and in vivo in rabbits. 10,11) It was shown that the controlled release intravaginal ring containing BRC was found to be effective to decrease the plasma prolactin level in rabbits.BRC has also used for the treatment of Parkinson disease and the transdermal administration may be more useful than vaginal administration, being not gender limited. Transdermal delivery of drugs is also very convenient from the application point of view and it offers several advantages over the other routes of drug administration and termination of the drug input is possible in problematic cases. 12,13) Transdermal systems represent one of the most successful non-oral systemic drug delivery system. However, because of limitations of the technology, the physical, chemical nature of the compounds and also lack of the knowledge about penetration mechanisms, transdermal drug delivery is not suited to all drugs and it needs to be justified for the therapies.14)The penetration mechanisms, histopathological hazards of the enhancers and vehicles need to be clarified.The aim of this study was to investigate an alternative delivery route for BRC. Several topical BRC gel formulations were developed using Carbopol (C-934), Daichitosan (CH) and Gantrez-SP215 (G-SP215) and applied to rabbits. Commercially available BRC tablets (Parlodel ® ) were also given to rabbits orally and plasma levels were compared. Two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol ® (TR) were also used to improve BRC penetration. Preparation of Gel Formulations For formation of the gel, CH or C-934 was dispersed in water then acetic acid or 0.01 N NaOH was added, respectively. BRC was dissolved in absolute ethanol and then mixed with the gel. TR or ST was added for the preparation of CH-ST or CH-TR gel. G-SP215 solution in ethanol was neutralised by triethanolamine and mixed with BRC solution in ethanol. Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumo...

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Effect of chitosan on epithelial permeability and structure

Cited by 494 publications

References 16 publications

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

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

Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes

Transdermal Administration of Bromocriptine.

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