51. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice
- Author
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M. Cristina L. Martins, André F. Maia, Ricardo Silva-Carvalho, Lia M. Costa, Catarina L. Seabra, Fátima Gärtner, Celso A. Reis, Pedro Oliveira, Inês C. Gonçalves, Susana Junqueira-Neto, Ana Magalhães, Bernardo Antunes, Joana Gomes, Paulo Costa, Eliette Touati, Patrícia C. Henriques, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Engenharia Biomédica [Porto, Portugal] (INEB), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Biologia Molecular e Celular - institute for molecular and cell biology [Porto, Portugal] (IBMC), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Faculdade de Medicina da Universidade do Porto (FMUP), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pharmaceutical Technology Laboratory [Porto], Faculdade de Farmácia da Universidade do Porto (FFUP), Universidade do Porto-Universidade do Porto, This work was financed by PTDC/CTM-BIO/4043/2014 and by Portuguese funds from FCT UID/BIM/04293/2019, UID/Multi/04378/2019, EXPL/CTM-BIO/0762/2013 and by L'OrealPortugal/FCT/UNESCO. Authors wish to thank FCT for Inês C. Gonçalves research position (IF/01479/2015), Patricia C. Henriques PhD grant (SFRH/BD/120154/2016) and Catarina L. Seabra PhD grant (SFRH/BD/89001/2012)., and The authors acknowledge the support of i3S Scientific Platforms, namely the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE), and the BioSciences Screening for the imaging data acquisition using equipment maintained by the platforms, both members of the PPBI (PPBI-POCI-01-0145-feder-022122), and CCGEN and Paula Magalhães, for the help during the PCR analysis.
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Bacteria adhesion ,0206 medical engineering ,Biomedical Engineering ,Mucoadhesion ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,02 engineering and technology ,Microparticles ,Biochemistry ,Microbiology ,Helicobacter Infections ,Biomaterials ,Mice ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,In vivo ,medicine ,Gastric mucosa ,Animals ,Humans ,[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials ,Molecular Biology ,Gastric Infection ,Gastrointestinal tract ,Chitosan ,biology ,Helicobacter pylori ,business.industry ,Stomach ,General Medicine ,021001 nanoscience & nanotechnology ,biology.organism_classification ,020601 biomedical engineering ,Mucus ,Microspheres ,3. Good health ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Gastric Mucosa ,0210 nano-technology ,business ,Ex vivo ,Biotechnology - Abstract
International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
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- 2019