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Tesi etd-06012022-003853


Tipo di tesi
Tesi di dottorato di ricerca
Autore
ZUCCHETTI, ERICA
URN
etd-06012022-003853
Titolo
Development of ophthalmic formulations and design of cell-based assays to evaluate their tolerability and efficacy
Settore scientifico disciplinare
CHIM/09
Corso di studi
SCIENZA DEL FARMACO E DELLE SOSTANZE BIOATTIVE
Relatori
tutor Prof.ssa Burgalassi, Susi
Parole chiave
  • stroma
  • permeation study
  • corneal epithalial cells
  • ophthalmic formulations
  • glaucoma
  • dry eye syndrome
  • nanomicells
  • liposomes
  • cornea construct
Data inizio appello
09/06/2022
Consultabilità
Non consultabile
Data di rilascio
09/06/2025
Riassunto
In this project three different topics were studied: possible formulations for the treatment of the Dry Eye Syndrome (DES) and Glaucoma and development of hydrogels to mimic corneal stroma in permeation studies.
For the DES section, three different formulations were developed and evaluated:
1) oleuropein (OLE) complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and encapsulated into a liposomal vesicular system in order to improve its stability. This formulation was tested for its protective activity from hyperosmotic stress and antioxidant activity on rabbit corneal epithelial cells.
2) Artificial eye-drops containing three ingredients : phospholipids, to restore the lipid layer of tear fluid; trehalose, as osmoprotectant molecule, and hyaluronic acid (HA), to keep the ocular surface moist. The aim of this project was to investigate the contribution of the individual components and any synergistic effects on dry eye protection and therefore an in vitro assay based on immortalized rabbit corneal epithelial cells was developed.
3) Cyclosporine-A (CyA) loaded nanomicellar formulation inside in situ gelling system to prolong the corneal contact time and improve the corneal penetration of the drug.
The Glaucoma section was focused on an inhibitor of monoacylglycerol lipase (MAGL) which is the main hydrolytic enzyme of 2-arachidonoylglycerol (2-AG) as possible anti-glaucoma molecule. In fact, the modulation of the 2-AG levels is a promising pharmacological strategy to activate the endocannabinoid system leading to a reduction of the intraocular pressure (IOP) and therefore a possible treatment in glaucoma, that is strictly related to an increment in IOP.
The section III is focused on the ethical problem of the large use of animals to test drugs and formulations. Hence, the study of possible artificial structures that simulate the cornea in permeation studies where the main barrier is the epithelium, but also the stroma plays an important role. For the native composition of the stroma, hydrogels seem promising structures as its substitutes in the development of an entire cornea construct. Therefore, this part of the project was focused on the preparation and characterization of different blends of hydrogels: polyvinyl alcohol/gelatin, polyvinyl alcohol/cellulose and chitosan hydrogels.
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