Transport of chitosan microparticles for mucosal vaccine delivery in a human intestinal M-cell model - PubMed

Transport of chitosan microparticles for mucosal vaccine delivery in a human intestinal M-cell model

I M van der Lubben et al. J Drug Target. 2002 Sep.

Abstract

Uptake of particulate antigen carrier systems by specialized M-cells of the gut-associated lymphoid tissue is still a limiting step in inducing efficient immune responses after oral vaccination. Although transport of soluble drugs over the epithelial barrier of the gut is extensively studied in vitro by using the Caco-2 cell model, this was for long time not possible for particles due to the absence of M-cells. By co-culturing Caco-2 cells with cultured human B-lymphocytes (Raji-cells), cells which are morphologically and functionally similar to M-cells can be induced. This human M-cells model makes it possible to study the uptake of microparticles for oral vaccine delivery. In this way, chitosan microparticles, which have demonstrated to target the Peyer's patches efficiently in vivo, could be tested in vitro. The development of this M-cells model facilitates the optimization of the microparticles in order to target them even more efficiently to the M-cells in the gut. In this study, the integrity of the human M-cell model was investigated by determining the transepithelial electrical resistance (TEER), 14C-mannitol transport and morphology using scanning electron microscopy. The uptake of particles was investigated by measuring transport of both fluorescently labeled microspheres (Fluospheres) and chitosan microparticles using flowcytometry. No discontinuities or abnormalities could be found in the co-culture. Scanning electron microscopy showed that morphologically different cells were present in the human M-cell model. Both commercially available Fluospheres (size 0.2 microm) and chitosan microparticles (size 1.7 microm) for oral vaccine delivery were transported at a significantly higher amount by the human M-cell model compared to the transport by the Caco-2 cell monoculture. Since chitosan microparticles were proven to be taken up by Peyer's patches in mice as well, this human M-cell model is able to predict the M-cell uptake of microparticles for oral vaccine delivery. This M-cell model is a new tool, which can be used to scan, develop and optimize microparticles for oral vaccine delivery. Since the M-cell uptake can now be studied in vitro, the targeting of these cells can be studied more efficiently and can now be done in cells from human origin.

Similar articles

• In vivo uptake of chitosan microparticles by murine Peyer's patches: visualization studies using confocal laser scanning microscopy and immunohistochemistry.

  Van Der Lubben IM, Konings FA, Borchard G, Verhoef JC, Junginger HE. Van Der Lubben IM, et al. J Drug Target. 2001;9(1):39-47. doi: 10.3109/10611860108995631. J Drug Target. 2001. PMID: 11378522

• Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine Peyer's patches.

  van der Lubben IM, Verhoef JC, van Aelst AC, Borchard G, Junginger HE. van der Lubben IM, et al. Biomaterials. 2001 Apr;22(7):687-94. doi: 10.1016/s0142-9612(00)00231-3. Biomaterials. 2001. PMID: 11246962

• A comparison of three Peyer's patch "M-like" cell culture models: particle uptake, bacterial interaction, and epithelial histology.

  Ahmad T, Gogarty M, Walsh EG, Brayden DJ. Ahmad T, et al. Eur J Pharm Biopharm. 2017 Oct;119:426-436. doi: 10.1016/j.ejpb.2017.07.013. Epub 2017 Jul 25. Eur J Pharm Biopharm. 2017. PMID: 28754262

• Chitosan for mucosal vaccination.

  van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. van der Lubben IM, et al. Adv Drug Deliv Rev. 2001 Nov 5;52(2):139-44. doi: 10.1016/s0169-409x(01)00197-1. Adv Drug Deliv Rev. 2001. PMID: 11718937 Review.

• [Oral vaccination and vaccine-entrapped microparticle delivery system].

  Li FQ, Fei YB, Su H, Hu JH. Li FQ, et al. Yao Xue Xue Bao. 2007 Mar;42(3):245-51. Yao Xue Xue Bao. 2007. PMID: 17520821 Review. Chinese.

Cited by

• Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review.

  Islam MA, Firdous J, Choi YJ, Yun CH, Cho CS. Islam MA, et al. Int J Nanomedicine. 2012;7:6077-93. doi: 10.2147/IJN.S38330. Epub 2012 Dec 13. Int J Nanomedicine. 2012. PMID: 23271909 Free PMC article. Review.

• Spray-dried mucoadhesive microspheres: preparation and transport through nasal cell monolayer.

  Harikarnpakdee S, Lipipun V, Sutanthavibul N, Ritthidej GC. Harikarnpakdee S, et al. AAPS PharmSciTech. 2006 Feb 10;7(1):E12. doi: 10.1208/pt070112. AAPS PharmSciTech. 2006. PMID: 16584142 Free PMC article.

• Physicochemical and immunological characterization of N,N,N-trimethyl chitosan-coated whole inactivated influenza virus vaccine for intranasal administration.

  Hagenaars N, Mastrobattista E, Verheul RJ, Mooren I, Glansbeek HL, Heldens JG, van den Bosch H, Jiskoot W. Hagenaars N, et al. Pharm Res. 2009 Jun;26(6):1353-64. doi: 10.1007/s11095-009-9845-y. Epub 2009 Feb 18. Pharm Res. 2009. PMID: 19224344

• Ultrastructural anatomy of CALT follicles in the rabbit reveals characteristics of M-cells, germinal centres and high endothelial venules.

  Knop N, Knop E. Knop N, et al. J Anat. 2005 Oct;207(4):409-26. doi: 10.1111/j.1469-7580.2005.00470.x. J Anat. 2005. PMID: 16191169 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information