Tesi etd-03032025-102909 |
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Tipo di tesi
Tesi di dottorato di ricerca
Autore
PAGANINI, VALENTINA
URN
etd-03032025-102909
Titolo
Design and Development of Advanced Skin and Eye Formulations for Targeted Drug Delivery: Innovative Experimental Models and Biopharmaceutical Evaluation
Settore scientifico disciplinare
CHEM-08/A - Tecnologia, socioeconomia e normativa dei medicinali e dei prodotti per il benessere e per la salute
Corso di studi
SCIENZA DEL FARMACO E DELLE SOSTANZE BIOATTIVE
Relatori
tutor Prof.ssa Chetoni, Patrizia
Parole chiave
- blue light
- corneal model
- drug permeation studies
- dry eye syndrome
- glaucoma
- hydrolipidic film
- in situ gelling system
- in vitro testing
- in vivo correlation
- melanoma
- nanomicelles
- oxidative stress
- solid lipid nanoparticles
- targeted drug delivery
Data inizio appello
10/03/2025
Consultabilità
Non consultabile
Data di rilascio
10/03/2028
Riassunto
This thesis focuses on the design of advanced formulations for targeted drug delivery, with a particular attention to their technological and physicochemical characterization, while also investigating innovative in vitro testing methods to predict biopharmaceutical behavior.
In the ophthalmic section, four distinct projects are presented. The first focuses on optimizing an in situ gelling system based on natural polymers—Gellan Gum and Arabinogalactan—for dry eye syndrome treatment. This formulation is extensively characterized, particularly to assess its behavior upon dilution with tear fluid after ocular administration. The second project, conducted under the supervision of Prof. Dr. Eliana B. Souto, involves the development and characterization of Carbachol-loaded solid lipid nanoparticles (SLNs) for glaucoma treatment. This preliminary study represents a significant innovation, as Carbachol—a highly hydrophilic, positively charged drug—has never been encapsulated in a lipophilic system, despite the potential benefits of such systems for topical ophthalmic therapy.
The third project focuses on the development of a novel 3D corneal model for drug permeation studies, incorporating a reconstructed corneal epithelium derived from rabbit corneal cells (RCE) and an artificial stroma, produced in collaboration with the University of Genova. Lastly, the fourth project introduces and validate a method to induce oxidative stress in an RCE cell line via Blue Light exposure, facilitating the screening of protective formulations and products against Blue Light.
The dermatological section shifts focus to the development of a thermosensitive hydrogel containing Curcumin-loaded nanomicelles for melanoma treatment. The nanomicelles, optimized for Curcumin solubilitization and cytotoxic effect on melanoma cells, demonstrate effective Curcumin accumulation in skin layers. Lastly, an innovative in vitro method to assess formulation affinity for the skin—using a simulated hydrolipidic film and contact angle measurements—is investigated and validated with a strong correlation with in vivo data.
In the ophthalmic section, four distinct projects are presented. The first focuses on optimizing an in situ gelling system based on natural polymers—Gellan Gum and Arabinogalactan—for dry eye syndrome treatment. This formulation is extensively characterized, particularly to assess its behavior upon dilution with tear fluid after ocular administration. The second project, conducted under the supervision of Prof. Dr. Eliana B. Souto, involves the development and characterization of Carbachol-loaded solid lipid nanoparticles (SLNs) for glaucoma treatment. This preliminary study represents a significant innovation, as Carbachol—a highly hydrophilic, positively charged drug—has never been encapsulated in a lipophilic system, despite the potential benefits of such systems for topical ophthalmic therapy.
The third project focuses on the development of a novel 3D corneal model for drug permeation studies, incorporating a reconstructed corneal epithelium derived from rabbit corneal cells (RCE) and an artificial stroma, produced in collaboration with the University of Genova. Lastly, the fourth project introduces and validate a method to induce oxidative stress in an RCE cell line via Blue Light exposure, facilitating the screening of protective formulations and products against Blue Light.
The dermatological section shifts focus to the development of a thermosensitive hydrogel containing Curcumin-loaded nanomicelles for melanoma treatment. The nanomicelles, optimized for Curcumin solubilitization and cytotoxic effect on melanoma cells, demonstrate effective Curcumin accumulation in skin layers. Lastly, an innovative in vitro method to assess formulation affinity for the skin—using a simulated hydrolipidic film and contact angle measurements—is investigated and validated with a strong correlation with in vivo data.
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