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Development of S-nitrosoglutathione loaded particles adapted to oral administration for preventing Inflammatory Bowel Disease relapses

Abstract : Inflammatory bowel diseases (IBD) (Crohn’s disease, ulcerative colitis…), are disabling pathologies affecting young patients and presenting the particularity that most of the current agents act by down regulating chronic inflammation in the intestine mucosa and cannot cure the disease. As the pivotal role of S-nitrosoglutathione (GSNO) in preventing intestinal inflammation and gut barrier failure has been clearly pointed out, therapies based on pharmaceutical technology to limit chronic inflammation and prevent relapses of barrier failure by an optimized dosage form of GSNO appears as an interesting challenge. The objective of this project relies on i) studying GSNO concentration/response functions in intestine by using Ussing chamber ex vivo model and following protein cell junction expression, ii) developing polymer nanocomposite particles encapsulating GSNO and adapted to the oral route, with GSNO protection, controlled delivery and local effect in intestine as major requirements. GSNO loaded polymeric (Eudragit® RL) nanoparticles were included in polymer matrix based on alginate; different processes were tested and particles were characterized: high GSNO loading, GSNO sustained release and local retention for 4 h in cellulo study (Caco-2) were obtained. Thus, therapies based on GSNO administration should represent a novel strategy to limit chronic inflammation and prevent relapses of barrier failure in IBD patients
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https://tel.archives-ouvertes.fr/tel-01835003
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Submitted on : Wednesday, July 11, 2018 - 10:06:56 AM
Last modification on : Sunday, October 25, 2020 - 7:06:03 AM
Long-term archiving on: : Friday, October 12, 2018 - 4:07:14 PM

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DDOC_T_2017_0325_MING.pdf
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  • HAL Id : tel-01835003, version 1

Citation

Hui Ming. Development of S-nitrosoglutathione loaded particles adapted to oral administration for preventing Inflammatory Bowel Disease relapses. Human health and pathology. Université de Lorraine, 2017. English. ⟨NNT : 2017LORR0325⟩. ⟨tel-01835003⟩

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