Corrado, Brunella
(2017)
DESIGN AND DEVELOPMENT OF A MICROFLUIDIC DEVICE FOR THE ASSESSMENT OF FIRST-PASS METABOLISM.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
DESIGN AND DEVELOPMENT OF A MICROFLUIDIC DEVICE FOR THE ASSESSMENT OF FIRST-PASS METABOLISM |
| Autori: |
| Autore | Email |
|---|
| Corrado, Brunella | brunella.corrado@unina.it |
|
| Data: |
10 Aprile 2017 |
| Numero di pagine: |
101 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Ingegneria Chimica, dei Materiali e della Produzione Industriale |
| Dottorato: |
Ingegneria dei prodotti e dei processi industriali |
| Ciclo di dottorato: |
29 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Mensitieri, Giuseppe | mensitie@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Netti, Paolo Antonio | [non definito] |
|
| Data: |
10 Aprile 2017 |
| Numero di pagine: |
101 |
| Parole chiave: |
First-pass metabolism; Organs-on-chip; Microfluidic; Liver-on-chip; Gut-on-chip; Air-liquid interface; 3D model; Drug screening |
| Settori scientifico-disciplinari del MIUR: |
Area 09 - Ingegneria industriale e dell'informazione > ING-IND/34 - Bioingegneria industriale |
[error in script]
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| Depositato il: |
25 Apr 2017 17:59 |
| Ultima modifica: |
08 Mar 2018 13:45 |
| URI: |
http://www.fedoa.unina.it/id/eprint/11801 |
| DOI: |
10.6093/UNINA/FEDOA/11801 |
Abstract
The aim of the thesis is to develop a microfluidic platform in order to mimic the first pass metabolism of oral ingested compounds. In the first part of the thesis, there is an introduction about the in vivo mechanism involved in the in process of first pass metabolism. First pass metabolism is strictly correlated to oral bioavailability of new developed drugs. The prediction of the dose of drug that reaches the blood flow and the target is fundamental. The organ involved in the first pass metabolism are principally the intestine, where a first metabolic process takes place, and the liver where the quote of drugs is metabolized again. New bioengineered in vitro model to assess first pass metabolism are explained, with a particular attention on 3D intestine and liver model. Furthermore, the first chapter is focused on the recent studies on organ-on-chip device that can recapitulate the in vivo physiology and microenvironment, with the relative steps of fabrications. To achieve the reproduction of the first pass metabolism on chip, we first focussed on the production of an innovative hepatic three dimensional tissues and then on the development of a organotypic intestinal tissues. In the chapter 2 it is presented the comparison of two kind of hepatic 3D model: spheroids and microtissues. The 3D-hepatic model chosen, was cultured into the new developed liver-on-chip device in order to have a perfusion culture.
The chapter 3 is focused on the fabrication of an organotypic intestinal 3D tissues cultured in both in static and dynamic conditions. In particular a gut-on-chip microfluidic device was fabricated in order to obtain an air-liquid interface culture. The combination of the two hepatic and intestine model on chip, is addressed in chapter 4. In this last chapter a microfluidic biochip, can accommodate both hepatic microtissues and 3D human intestinal equivalent. By the selective communication of the two tissues recreated into the biochip, it is possible to simulate in vitro the mechanism of orally ingested drugs.
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