In recent times, drug delivery systems (DDS) have proved to be one of the most promising applications in the biomedical and pharmaceutical fields. They are currently the subject of extensive research and are created in order to improve the pharmacokinetics and pharmacodynamics of drugs and to allow their transport to the target site in the desired dose, at the right time and with the appropriate rate of release. This thesis reports a comparative study of organic-inorganic hybrid systems, with possible application in the field of drug delivery. The objective of this work is therefore to find the best combination between the two components of the hybrid, in order to obtain an improvement in the pharmacokinetic and pharmacological properties of the drug. For this purpose, the experimental part began with the synthesis of different biomaterials as drug carriers, varying the experimental conditions for their obtaining and studying their effects on drug loading and pharmacological efficacy. The synthesized inorganic component is represented by inorganic calcium phosphates such as hydroxyapatite and brushite. As model drugs on which to carry out the comparative study, Bumetanide and Perfenazine were chosen, as they are poorly soluble drugs in water and with low dissolution rates of the active ingredient. It was then preferred to focus on the drug Bumetanide, as the Brushite-Bumetanide and Nanorods-Bumetanide hybrids obtained gave excellent results from dissolution studies. The formation of the hybrids was demonstrated by SEM electron microscopy analysis coupled with EDS microanalysis (showing a homogeneous distribution of the elements of the components of the hybrid) and FT-IR spectroscopy. The drug was adsorbed on the surface of hydroxyapatite and Brushite in amorphous form, as demonstrated by X-ray diffraction of powders (XRPD) and its thermal stability was confirmed by hybrid differential scanning calorimetry (DSC), of the melting peaks. and decomposition typical of the drug. The dissolution tests carried out on the hybrid compounds showed a notable improvement over the drug alone in terms of dissolution rate in all the fluids tested. These evidences suggest that these organic-inorganic hybrids, suitably optimized, represent an extremely simple, safe, fast and inexpensive system to implement and to be used in the future also for types of drugs.
Negli ultimi tempi, i sistemi di drug delivery (DDS) sono risultati una delle applicazioni più promettenti in ambito biomedico e farmaceutico. Sono attualmente oggetto di numerose ricerche e vengono creati in modo da migliorare la farmacocinetica e la farmacodinamica dei farmaci e da consentire il loro trasporto al sito bersaglio nella dose desiderata, al momento opportuno e con l’adeguata velocità di rilascio. La presente tesi riporta uno studio comparativo di sistemi ibridi organici-inorganici, con possibile applicazione nel campo del drug delivery. L’obiettivo di questo lavoro è dunque, trovare la migliore combinazione tra le due componenti dell’ibrido, al fine di ottenere un miglioramento delle proprietà farmacocinetiche e farmacologiche del farmaco. A tale scopo, la parte sperimentale ha avuto inizio con la sintesi di diversi biomateriali come carrier di farmaci, andando a variare le condizioni sperimentali per il loro ottenimento e studiandone gli effetti sul caricamento del farmaco e l’efficacia farmacologica. La componente inorganica sintetizzata è rappresentata da fosfati di calcio inorganici quali idrossiapatite e brushite. Come farmaci modello su cui effettuare lo studio comparativo, sono stati scelti la Bumetanide e Perfenazina, in quanto farmaci scarsamente solubili in acqua e con bassi tassi di dissoluzione del principio attivo. Si è preferito poi, concentrarsi sul farmaco Bumetanide, in quanto gli ibridi Brushite-Bumetanide e Nanorods-Bumetanide ottenuti, hanno dato degli ottimi risultati dagli studi di dissoluzione. La formazione degli ibridi è stata dimostrata mediante analisi di microscopia elettronica SEM accoppiata con microanalisi EDS (che mostra una distribuzione omogenea degli elementi dei componenti dell’ibrido) e spettroscopia FT-IR. Il farmaco è stato adsorbito sulla superficie dell’ idrossiapatite e Brushite in forma amorfa, come dimostrato dalla diffrazione a raggi X di polveri (XRPD) e la sua stabilità termica è stata confermata mediante calorimetria differenziale a scansione (DSC) grazie all’assenza, negli ibridi, dei picchi di fusione e decomposizione tipici del farmaco. I test di dissoluzione effettuati sui composti ibridi hanno mostrato un notevole miglioramento rispetto al solo farmaco in termini di velocità di dissoluzione in tutti i fluidi testati. Queste evidenze suggeriscono che tali ibridi organici-inorganici, opportunamente ottimizzati, rappresentano un sistema estremamente semplice, sicuro, veloce e poco costoso da realizzare e da impiegare in futuro anche per altre tipologie di farmaci.
Studio comparativo di sistemi ibridi organici-inorganici per drug delivery: l'importanza delle condizioni sperimentali e l'effetto sull'efficacia
DI STEFANO, DEBORAH
2021/2022
Abstract
In recent times, drug delivery systems (DDS) have proved to be one of the most promising applications in the biomedical and pharmaceutical fields. They are currently the subject of extensive research and are created in order to improve the pharmacokinetics and pharmacodynamics of drugs and to allow their transport to the target site in the desired dose, at the right time and with the appropriate rate of release. This thesis reports a comparative study of organic-inorganic hybrid systems, with possible application in the field of drug delivery. The objective of this work is therefore to find the best combination between the two components of the hybrid, in order to obtain an improvement in the pharmacokinetic and pharmacological properties of the drug. For this purpose, the experimental part began with the synthesis of different biomaterials as drug carriers, varying the experimental conditions for their obtaining and studying their effects on drug loading and pharmacological efficacy. The synthesized inorganic component is represented by inorganic calcium phosphates such as hydroxyapatite and brushite. As model drugs on which to carry out the comparative study, Bumetanide and Perfenazine were chosen, as they are poorly soluble drugs in water and with low dissolution rates of the active ingredient. It was then preferred to focus on the drug Bumetanide, as the Brushite-Bumetanide and Nanorods-Bumetanide hybrids obtained gave excellent results from dissolution studies. The formation of the hybrids was demonstrated by SEM electron microscopy analysis coupled with EDS microanalysis (showing a homogeneous distribution of the elements of the components of the hybrid) and FT-IR spectroscopy. The drug was adsorbed on the surface of hydroxyapatite and Brushite in amorphous form, as demonstrated by X-ray diffraction of powders (XRPD) and its thermal stability was confirmed by hybrid differential scanning calorimetry (DSC), of the melting peaks. and decomposition typical of the drug. The dissolution tests carried out on the hybrid compounds showed a notable improvement over the drug alone in terms of dissolution rate in all the fluids tested. These evidences suggest that these organic-inorganic hybrids, suitably optimized, represent an extremely simple, safe, fast and inexpensive system to implement and to be used in the future also for types of drugs.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/14526