This experimental project is part of a drug repurposing strategy aimed at the topical application of API-X for the treatment of cutaneous conditions characterized by fibrotic, hypertrophic, and edematous alterations. The objective of this study was to evaluate the technological feasibility of an innovative platform for the delivery of API-X, based on polymeric matrices produced by electrospinning and containing active-loaded particulate systems (Ps). Different characteristics of the particulate systems were investigated in order to assess their influence of the properties of the developed formulations. In the first phase, a preformulation study of API-X was conducted to evaluate its solubility and stability under the experimental conditions of interest. Subsequently, an HPLC-UV method was developed and optimized for the quantification of the active ingredient by evaluating calibration curves under different experimental conditions. The method showed a good correlation between concentration and chromatographic response, allowing the reproducible determination of API-X. The electrospun formulations were then produced and characterized according to the characteristics of the particulate systems and their incorporation percentage. Macroscopic characterization highlighted differences in the mechanical and surface properties of the formulations, which maintained good structural integrity. Morphological characterization by scanning electron microscopy (SEM), also performed following exposure to the experimental conditions of interest, revealed progressive modifications of the fibrous architecture, indicative of interactions between the formulations and the surrounding medium. The drug content of the formulations was also determined in order to quantify the amount of API-X effectively incorporated into the system, and its distribution within the formulations was evaluated. Finally, an in vitro release study was conducted under simulated physiological conditions to characterize the release profile of API-X and to assess the influence of the formulation characteristics on the behaviour of the system. Overall, the results obtained demonstrate the technological feasibility of the developed platform for the incorporation and release of API-X and indicate that the characteristics of the particulate systems may influence the structural properties of the electrospun formulations and their behaviour under simulated physiological conditions. The platform therefore represents a promising experimental system for further optimization studies and subsequent biological evaluation, aimed the exploring its potential in cutaneous conditions characterized by fibrotic alterations.
Il presente lavoro di tesi sperimentale si inserisce nell’ambito di una strategia di Drug Repurposing finalizzata all’impiego topico di API-X nel trattamento di condizioni cutanee caratterizzate da alterazioni fibrotiche, ipertrofiche ed edematose. L’obiettivo dello studio è stato valutare la fattibilità tecnologica di una piattaforma innovativa per il rilascio di API-X, basata su matrici polimeriche ottenute mediante elettrofilatura e contenenti sistemi particellari (Ps) caricati con l’attivo. Sono state investigate differenti caratteristiche dei sistemi particellari, al fine di valutarne l’influenza sulle proprietà delle formulazioni sviluppate. In una prima fase è stato condotto uno studio preformulativo di API-X, finalizzato alla valutazione delle sue caratteristiche di solubilità e stabilità nelle condizioni sperimentali di interesse. Successivamente è stato sviluppato e ottimizzato un metodo HPLC-UV per la quantificazione dell’attivo, mediante la valutazione di curve di calibrazione in differenti condizioni sperimentali. Il metodo ha mostrato una buona correlazione tra concentrazione e risposta cromatografica, consentendo la determinazione riproducibile di API-X. Le formulazioni elettrofilate sono state quindi prodotte e caratterizzate in funzione delle caratteristiche dei sistemi particellari e della loro percentuale di incorporazione. La caratterizzazione macroscopica ha evidenziato differenze nelle proprietà meccaniche e superficiali delle formulazioni, che hanno mantenuto una buona integrità strutturale. La caratterizzazione morfologica mediante microscopia elettronica a scansione (SEM), condotta anche dopo esposizione alle condizioni sperimentali di interesse, ha evidenziato modificazioni progressive della architettura fibrosa, indicative dell’interazione delle formulazioni con il mezzo circostante. È stato inoltre determinato il drug content delle formulazioni, al fine di quantificare la quantità di API-X effettivamente incorporata, e ne è stata valutata la distribuzione all’interno del sistema. Infine, è stato condotto uno studio di rilascio in vitro in condizioni fisiologiche simulate, volto a caratterizzare il profilo di rilascio di API-X e a valutare l’influenza delle caratteristiche formulative sul comportamento del sistema. Nel complesso, i risultati ottenuti dimostrano la fattibilità tecnologica della piattaforma sviluppata per l’incorporazione e il rilascio di API-X e indicano che le caratteristiche dei sistemi particellari possono influenzare le proprietà strutturali delle formulazioni elettrofilate e il loro comportamento in ambiente fisiologico simulato. La piattaforma rappresenta pertanto una sistema sperimentale di interesse per ulteriori studi di ottimizzazione e per la successiva valutazione biologica, finalizzati ad esplorarne il potenziale impiego topico nell’ambito di condizioni cutanee caratterizzate da alterazioni fibrotiche.
Sviluppo di piattaforme polimeriche per la veicolazione locale di API-X nell’ambito del Drug Repurposing
VERENINI, BENEDETTA
2025/2026
Abstract
This experimental project is part of a drug repurposing strategy aimed at the topical application of API-X for the treatment of cutaneous conditions characterized by fibrotic, hypertrophic, and edematous alterations. The objective of this study was to evaluate the technological feasibility of an innovative platform for the delivery of API-X, based on polymeric matrices produced by electrospinning and containing active-loaded particulate systems (Ps). Different characteristics of the particulate systems were investigated in order to assess their influence of the properties of the developed formulations. In the first phase, a preformulation study of API-X was conducted to evaluate its solubility and stability under the experimental conditions of interest. Subsequently, an HPLC-UV method was developed and optimized for the quantification of the active ingredient by evaluating calibration curves under different experimental conditions. The method showed a good correlation between concentration and chromatographic response, allowing the reproducible determination of API-X. The electrospun formulations were then produced and characterized according to the characteristics of the particulate systems and their incorporation percentage. Macroscopic characterization highlighted differences in the mechanical and surface properties of the formulations, which maintained good structural integrity. Morphological characterization by scanning electron microscopy (SEM), also performed following exposure to the experimental conditions of interest, revealed progressive modifications of the fibrous architecture, indicative of interactions between the formulations and the surrounding medium. The drug content of the formulations was also determined in order to quantify the amount of API-X effectively incorporated into the system, and its distribution within the formulations was evaluated. Finally, an in vitro release study was conducted under simulated physiological conditions to characterize the release profile of API-X and to assess the influence of the formulation characteristics on the behaviour of the system. Overall, the results obtained demonstrate the technological feasibility of the developed platform for the incorporation and release of API-X and indicate that the characteristics of the particulate systems may influence the structural properties of the electrospun formulations and their behaviour under simulated physiological conditions. The platform therefore represents a promising experimental system for further optimization studies and subsequent biological evaluation, aimed the exploring its potential in cutaneous conditions characterized by fibrotic alterations.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14239/37161