Polymeric composite systems and nanomedicine are rising strategies used especially in regenerative medicine. A lot of interest was devoted in studying hydrogels for both cell and drug delivery, creating new biocompatible and biodegradable three-dimensional polymer networks able to directly entrap nanoparticles (NPs) containing drugs, and to permit their controlled release. In this thesis, new hydrogel formulations with the addition of carboxymethyl cellulose (CMC) as natural polymer are investigated from the chemical and physical point of view, in order to create a completely new natural hydrogel. Given that hydrogels can carry only hydrophilic drugs, they are used as NPs scaffolds in order to achieve a best therapeutic effect in situ. Thus, these composite systems exploit in the best way the properties of both hydrogels and NPs, in particular the tendency to swell of the first and the ability to diffuse almost everywhere, due to the very small dimensions, of the latter. Studying these two components it is possible to modulate the system release capability in various pH environments, to avoid both under and overdosing of drugs. Two different pH conditions are considered because if an oral route of administration is used, the polymeric system has to pass not only in neutral pH zones of the human body but also in the stomach or in the gastrointestinal apparatus, which are characterized by very acid environments. In this way, advantages and drawbacks of different CMC formulations of hydrogels are investigated, and also an approximation of the 3D mesh size is hypothesized.
I sistemi compositi polimerici e le nanomedicine sono strategie emergenti usate principalmente nella medicina rigenerativa. Lo studio degli idrogeli ha suscitato molto interesse per il rilascio sia di farmaci che di cellule, poiché viene creato un reticolo tridimensionale con nuovi polimeri biocompatibili e biodegradabili, in grado di intrappolare nanoparticelle contenenti farmaci, e quindi permettere il loro controllato rilascio nel corpo di interesse. In questo studio di tesi sono state investigate dal punto di vista fisico e chimico nuove formulazioni di idrogeli, utilizzando in aggiunta la carbossimetilcellulosa, come fonte polimerica naturale, così da creare un nuovo idrogel completamente naturale. Siccome gli idrogeli possono trasportare solamente farmaci idrofili, essi vengono utilizzati come supporto per il trasporto delle nanoparticelle in modo da raggiungere in situ il miglior effetto terapeutico. Questi sistemi compositi sfruttano nel miglior modo le proprietà sia degli idrogeli che delle nanoparticelle, in particolare viene sfruttata la tendenza a rigonfiare (swelling) dei primi e l’abilità di diffondere pressoché ovunque dei secondi, grazie alle loro ridotte dimensioni. Studiando questi due componenti è possibile modulare la capacità del sistema di rilasciare anche in diverse condizioni esterne di pH, in modo da evitare un sotto o sovra dosaggio del farmaco. Sono state considerate due diverse condizioni di pH, poiché se il sistema venisse somministrato oralmente esso non attraverserebbe solo le zone a pH neutro, ma anche zone molto acide, come lo stomaco o l’apparato gastrointestinale. Così sono stati evidenziati vantaggi e svantaggi delle diverse formulazioni, e in base ai risultati è stata fatta un’approssimazione sulla grandezza di maglia del reticolo tridimensionale.
Polymeric composite systems based on carboxymethyl cellulose for controlled drug delivery
REBELLATO, ERICA
2016/2017
Abstract
Polymeric composite systems and nanomedicine are rising strategies used especially in regenerative medicine. A lot of interest was devoted in studying hydrogels for both cell and drug delivery, creating new biocompatible and biodegradable three-dimensional polymer networks able to directly entrap nanoparticles (NPs) containing drugs, and to permit their controlled release. In this thesis, new hydrogel formulations with the addition of carboxymethyl cellulose (CMC) as natural polymer are investigated from the chemical and physical point of view, in order to create a completely new natural hydrogel. Given that hydrogels can carry only hydrophilic drugs, they are used as NPs scaffolds in order to achieve a best therapeutic effect in situ. Thus, these composite systems exploit in the best way the properties of both hydrogels and NPs, in particular the tendency to swell of the first and the ability to diffuse almost everywhere, due to the very small dimensions, of the latter. Studying these two components it is possible to modulate the system release capability in various pH environments, to avoid both under and overdosing of drugs. Two different pH conditions are considered because if an oral route of administration is used, the polymeric system has to pass not only in neutral pH zones of the human body but also in the stomach or in the gastrointestinal apparatus, which are characterized by very acid environments. In this way, advantages and drawbacks of different CMC formulations of hydrogels are investigated, and also an approximation of the 3D mesh size is hypothesized.File | Dimensione | Formato | |
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https://hdl.handle.net/10589/137487