This thesis presents an extended work concerning the development of lipid-based systems able to prevent and control the ocular diseases associated with oxidative stress. The eye drops dosage forms account for nearly 90% of currently available marketed formulations thanks of their simplicity, safety and acceptance by patients. However, the bioavailability of topically applied drugs is about 5%. The lipid-based nanocarriers, which are highly biocompatible, can carry the antioxidant to the specific site. Among the antioxidants used for ophthalmic applications, the attention was focused on Epigallocatechin-3-gallate and Edaravone molecules, which are well-known for being bioactive in ocular diseases associated with oxidative stress. Since the final aim was to create a stable and efficient delivery system, the design of lipid-based nanocarriers has been based on three critical targets: a) High encapsulation efficiency in order to optimize the delivery of the active principle at the target sites. b) Colloidal stability and characterization of lipid-based systems. c) Ability to protect the retinal cells from oxidative stress-induced cell death. From the obtained results, we concluded that the encapsulation percentage of EGCG inside liposomes showed specific ion effects together with influence of the lipid matrix composition. More in details, the combination of magnesium chloride, anionic matrix and Poloxamer-407 allow us to obtain a system highly stable with 100% EGCG encapsulation that was able to protect retinal cells from oxidative stress. Using increasing concentrations of EGCG we optimized the encapsulation efficiency of catechin inside the cubic and hexagonal phase, others interesting systems used in the ophthalmic field. The structures of all systems were characterized by X-Ray and Neutrons experiments. In addition, the introduction of lipophilic C-18 chain in EGCG and Edaravone molecules also increased their encapsulation efficiency inside a liposomal vector as well as their ability to protect the retinal cells from oxidative stress.
Le principali forme farmaceutiche per uso oftalmico sono rappresentate dai colliri grazie alla loro semplicità di preparazione, sterilizzazione e somministrazione. Tuttavia, i colliri presentano una bassa biodisponibilità di circa il 5%. Ottimi risultati si sono ottenuti con l’utilizzo di sistemi di veicolazione di farmaci a base lipidica caratterizzati da elevata biocompatibilità. La nostra attenzione è stata rivolta all’utilizzo di due diverse molecole con potente potenziale antiossidante, l’Epigallocatechina-3-gallato (EGCG) e l’Edaravone, le quali hanno dimostrato la loro efficacia nel trattamento e/o prevenzione delle patologie oculari associate allo stress ossidativo. L’obbiettivo finale è lo sviluppo di un sistema di veicolazione di farmaci stabile ed efficiente considerando 3 punti fondamentali: (a) Massimizzare la quantità di farmaco inglobata nel sistema di trasporto lipidico al fine aumentare la quantità di molecola che giunge al sito target. ( b) Stabilità colloidale e caratterizzazione dei sistemi di trasporto. (c) Abilità di proteggere le cellule retinale dalla morte cellulare indotta dallo stress ossidativo. Dai risultati ottenuti possiamo concludere che la percentuale di inglobamento della molecola EGCG risente dell’effetto salino e della composizione lipidica. In particolare, l’utilizzo di MgCl2 in combinazione con una matrice anionica ed, in presenza del Poloxamer-407, ci ha permesso di ottenere un sistema altamente stabile caratterizzato dal 100% di inglobamento. Questo sistema si è dimostrato capace di proteggere le cellule retinali dallo stress ossidativo in misura maggiore rispetto alla molecola veicolata tal quale. L’utilizzo di concentrazioni crescenti ci ha permesso di aumentare l’inglobamento dell’EGCG all’interno di fasi cubiche ed esagonali, altri sistemi di veicolazione di farmaci usati in campo oftalmico. La struttura di tutti i sistemi studiati è stata caratterizzata mediante esperimenti di diffrazione a raggi x e neutroni. Inoltre, l’introduzione di gruppi lipofili costituiti da catene di C-18, oltre a permettere il completo inglobamento delle molecole studiate, ha aumentato la loro capacità di proteggere le cellule retinale dalla morte indotta dallo stress ossidativo.
Natural and Functionalized Molecules with Antioxidant and Scavenging Activity as Components of Innovative Lipid-based Artificial Tears / Minnelli, Cristina. - (2019 Mar 05).
Natural and Functionalized Molecules with Antioxidant and Scavenging Activity as Components of Innovative Lipid-based Artificial Tears
MINNELLI, CRISTINA
2019-03-05
Abstract
This thesis presents an extended work concerning the development of lipid-based systems able to prevent and control the ocular diseases associated with oxidative stress. The eye drops dosage forms account for nearly 90% of currently available marketed formulations thanks of their simplicity, safety and acceptance by patients. However, the bioavailability of topically applied drugs is about 5%. The lipid-based nanocarriers, which are highly biocompatible, can carry the antioxidant to the specific site. Among the antioxidants used for ophthalmic applications, the attention was focused on Epigallocatechin-3-gallate and Edaravone molecules, which are well-known for being bioactive in ocular diseases associated with oxidative stress. Since the final aim was to create a stable and efficient delivery system, the design of lipid-based nanocarriers has been based on three critical targets: a) High encapsulation efficiency in order to optimize the delivery of the active principle at the target sites. b) Colloidal stability and characterization of lipid-based systems. c) Ability to protect the retinal cells from oxidative stress-induced cell death. From the obtained results, we concluded that the encapsulation percentage of EGCG inside liposomes showed specific ion effects together with influence of the lipid matrix composition. More in details, the combination of magnesium chloride, anionic matrix and Poloxamer-407 allow us to obtain a system highly stable with 100% EGCG encapsulation that was able to protect retinal cells from oxidative stress. Using increasing concentrations of EGCG we optimized the encapsulation efficiency of catechin inside the cubic and hexagonal phase, others interesting systems used in the ophthalmic field. The structures of all systems were characterized by X-Ray and Neutrons experiments. In addition, the introduction of lipophilic C-18 chain in EGCG and Edaravone molecules also increased their encapsulation efficiency inside a liposomal vector as well as their ability to protect the retinal cells from oxidative stress.File | Dimensione | Formato | |
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Tesi_Minnelli.pdf
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