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Design and development of a biocompatible nanocomposite as oral drug delivery system for the treatment of inflammatory bowel diseases

Giulia Guerriero

Design and development of a biocompatible nanocomposite as oral drug delivery system for the treatment of inflammatory bowel diseases.

Rel. Clara Mattu, Giovanna Lollo. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2022

Abstract:

Oral delivery is recognized as the preferred route of administration for most drugs due to its unique advantages, including the possibility of self-administration and flexibility in dosage regimen improving patient compliance, and the availability of an extensive gastrointestinal (GI) surface area for drug absorption. Nevertheless, the oral route is characterized by the presence of several obstacles such as rapid clearance and biological barriers, that can hamper an efficient drug delivery. These challenges may be exceeded developing drug delivery systems able to enhance local drug efficacy by either passive or active targeting. Orally administrated drug delivery systems have gained a great deal of attention as carriers for the local treatment of Inflammatory Bowel Diseases (IBDs). IBDs, such as Crohn’s disease and ulcerative colitis, are highly debilitating pathologies associated with the imbalance of inflammatory mediators within the inflamed bowel that required life-lasting treatments. In IBDs, oral drug delivery drawbacks are amplified by an inter- and intra-patient variability due to GI physiology alterations caused by the chronic inflammation, such as the loss of the intestinal epithelium integrity and inconsistent inefficacy of treatments. Conventional drugs for IBDs treatment include anti-inflammatory medications and immune suppressants, which suffer from a lack of bioavailability and high dose-induced systemic side effects. Innovative strategies are thus needed to improve therapy adherence and patient’s quality of life. With the purpose of increasing local drug therapeutic efficacy, nanoparticles have been tailored for the delivery of active molecules into the inflamed tissue by exerting an epithelial enhanced permeability and retention effect and for the preferential uptake by the immune cells. In the present work, to increase the residence time in the GI tract, nanoparticles have been complexed with bioadhesive matrixes, creating nanocomposites. Anionic polymers have been selected to preferentially adhere to the inflamed tissue via electrostatic interactions due to the high concentration of positively charged proteins in inflamed regions, and thus assisting site-specific targeting and enhancing nanoparticles permeation. Accordingly, the aim of the present work is the development and the design of an oral drug delivery nanocomposite for IBD treatment. Nanoemulsions (NEs) have been successfully prepared by microfluidic for the encapsulation of tofacitinib, a small hydrophobic molecule approved for the treatment of autoimmune diseases, such as IBD. Then, alginate microbeads have been designed to bioadhere to the inflamed tissue and to release the embedded NE, designed to penetrate the epithelium and to release the active. The results obtained highlighted the possibility of creating a nanocomposite system with tailored characteristics for the localized treatment of IBDs. Mucopenetrating properties of NEs have been confirmed by in vitro studies on a co-culture of CACO/HT-29 cells. Ex-vivo studies on rat colon mucosa have shown a high percentage of nanocomposite retained by the mucosal tissue when compared to the NEs alone, confirming its mucoadhesive properties. In vivo studies on colitis mice models are planned to confirm the nanocomposite preferential accumulation at the diseased site, followed by pharmacokinetic studies to evaluate the reduction of the drug concentration in the systemic circulation, while not affecting its local efficacy.

Relatori: Clara Mattu, Giovanna Lollo
Anno accademico: 2021/22
Tipo di pubblicazione: Elettronica
Numero di pagine: 81
Informazioni aggiuntive: Tesi secretata. Fulltext non presente
Soggetti:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: Nuovo ordinamento > Laurea magistrale > LM-21 - INGEGNERIA BIOMEDICA
Aziende collaboratrici: Université de Lyon
URI: http://webthesis.biblio.polito.it/id/eprint/23805
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