Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation-responsive nanoparticles (NPs) are formulated from a phenylboronic esters-modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H2O2). OxiDEX NPs are coated with chitosan and encapsulated in a pH-sensitive polymer to produce nano-in-micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H2O2, and the release of the drug is sustained in the presence of physiologically relevant H2O2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29-MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano-in-micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.

pH and Reactive Oxygen Species-Sequential Responsive Nano-in-Micro Composite for Targeted Therapy of Inflammatory Bowel Disease

Bertoni, Serena;Albertini, Beatrice;Passerini, Nadia
;
2018

Abstract

Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation-responsive nanoparticles (NPs) are formulated from a phenylboronic esters-modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H2O2). OxiDEX NPs are coated with chitosan and encapsulated in a pH-sensitive polymer to produce nano-in-micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H2O2, and the release of the drug is sustained in the presence of physiologically relevant H2O2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29-MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano-in-micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.
Bertoni, Serena; Liu, Zehua; Correia, Alexandra; Martins, João Pedro; Rahikkala, Antti; Fontana, Flavia; Kemell, Marianna; Liu, Dongfei; Albertini, Beatrice; Passerini, Nadia*; Li, Wei; Santos, Hélder A.
File in questo prodotto:
File Dimensione Formato  
Reactive oxygen species-responsive nano-in-micro composite for targeted therapy of inflammatory bowel disease.pdf

embargo fino al 16/10/2019

Descrizione: Accepted manuscript
Tipo: Postprint
Licenza: Licenza per accesso libero gratuito
Dimensione 2.02 MB
Formato Adobe PDF
2.02 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/664018
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 47
social impact