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International Journal of PharmaceuticsVolume 454, Issue 1, 2013, Pages 116-124

Modulation of stability and mucoadhesive properties of chitosan microspheres for therapeutic gastric application(Article)

  • aINEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
  • bIPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Portugal
  • cUniversidade do Porto, Faculdade de Engenharia, Porto, Portugal
  • dUniversidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal

Abstract

Chitosan microspheres have been explored for pharmaceutical applications, namely as a drug delivery systems for Helicobacter pylori gastric infection treatment, due to their mucoadhesive capacity. In this study, a different application of chitosan microspheres is proposed aiming the creation of an H. pyloribinding system where, after oral administration, microspheres will capture and remove these bacteria from infected patients, taking advantage of their muco/bacterial adhesive process. However, mucoadhesion is influenced by the degree of crosslinking necessary to avoid microspheres dissolution in the acidic gastric environment. During this work, the effect of genipin crosslinking on the stability, size, charge and mucoadhesive properties of chitosan microspheres under acidic pH was studied. Chitosan microspheres with ∼170 μm were produced by ionotropic gelation and subsequently covalently crosslinked with genipin in different degrees. The crosslinking reaction was followed by infrared spectroscopy and time-lapse fluorescence microscopy, since we have demonstrated that the fluorescence intensity of chitosan microspheres increases with genipin chemical bonding to chitosan. Results showed that both the zeta potential and the swelling capacity of chitosan microspheres decrease with increasing crosslinking. When immersed in simulated gastric fluid (SGF) with pepsin for 7 days, chitosan microspheres crosslinked with 10 mM of genipin for 1 h did not dissolve and doubled their size to approximately 345 μm. Furthermore, they maintained their in vitro mucoadhesion to soluble gastric mucins at both pH tested (3.6 and 6.5) and presented an in vivo retention time of around 2 h in the stomach of C57BL/6 mice. © 2013 Elsevier B.V. All rights reserved.

Author keywords

BiomaterialsChitosanGenipinHelicobacter pyloriMicrospheresMucoadhesion

Indexed keywords

EMTREE drug terms:chitosangenipinmicrospherepepsin Astomach mucin
EMTREE medical terms:acidityanimal experimentarticlechemical bindingdrug stabilityfluorescence microscopygelationHelicobacter pyloriinfrared spectroscopymousemucoadhesionnonhumanparticle sizepriority journalstomach juicezeta potential

Chemicals and CAS Registry Numbers:

chitosan, 9012-76-4; genipin, 6902-77-8; pepsin A, 9001-75-6; stomach mucin, 9007-86-7

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de CompetitividadeCOMPETE
Fundação para a Ciência e a Tecnologia
See opportunities
Sapienza Università di Roma
Fundação para a Ciência e a Tecnologia
See opportunities
PTDC/CTM/65330/2006,PTDC/CTM-BPC/121149/2010,SFRH/BPD/63722/2009,FCOMP-01-0124-FEDER-020073,PEst-C/SAU/LA0002/2011
  • 1

    This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT) in the framework of the projects PEst-C/SAU/LA0002/2011, FCOMP-01-0124-FEDER-020073, PTDC/CTM/65330/2006 and PTDC/CTM-BPC/121149/2010. Inês C. Gonçalves is grateful to FCT for the grant SFRH/BPD/63722/2009 and to Sofia Lamas from the animal house facility of IBMC/INEB for the support in the in vivo experiments. Stefania Nardecchia is grateful for the grant of the “Sapienza” Università di Roma, Italy.

  • ISSN: 03785173
  • CODEN: IJPHD
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.ijpharm.2013.06.068
  • PubMed ID: 23850814
  • Document Type: Article
  • Publisher: Elsevier B.V.

  Martins, M.C.L.; INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, Portugal;
© Copyright 2017 Elsevier B.V., All rights reserved.

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View details of all 33 citations
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