Schema de realizare a proiectului 23 03 01 - Anul 2025 - Etapa I
Contractul nr.: 30N/12.01.2023
Proiectul: "Dezvoltarea de solutii inovatoare si tehnologii de fabricație avansată cu laseri, plasmă și radiații pentru rezolvarea problemelor societale"
Faza 13/2025: "Studii experimentale și analitice pentru dezvoltarea de pansamente de tip hidrogel încărcate cu medicamente chimioterapeutice"
Responsabil fază: Dr. Maria DEMETER, Dr. Angela STAICU
Termen de încheiere a fazei: 09.04.2025
Abstract:
Multifunctional drug delivery systems are a new strategy in targeted cancer treatment, as they offer the advantage of delivering chemotherapeutic without affecting healthy cells and tissues. In this study, new polymeric compositions obtained from poly(vinylpyrrolidone), carboxymethylcellulose, poly(ethylene glycol), agar, and gellan gum were produced and characterized to develop hydrogel dressings loaded with chemotherapeutic drugs. The hydrogels were simultaneously synthesized (cross-linked) and sterilized by electron beam irradiation at a dose of 30 kGy. The functionality of the hydrogels was achieved through: sol-gel analysis, efficiency of the crosslinking process, swelling properties in simulated physiological and tumor environments, moisture retention capacity, structural analysis (ATR-FTIR), rheological properties, in vitro biodegradation, anticancer 5-FU drug loading capacity, and in vitro release profile of 5-FU. The release kinetics of 5-FU were investigated using mathematical models commonly employed in the design of pharmaceutical formulations. After irradiation, the hydrogels have a gel fraction of over 90%, and the crosslinking process predominates. The increased values of radiochemical yields of crosslinking (330 µmol/J), 16 times higher compared to those of degradation (20 µmol/J), confirm the formation of crosslinked hydrogels with a stable structure after irradiation. The swelling medium significantly influences the degree of swelling and the 5-FU loading capacity of the hydrogels. In a basic environment, the absorption capacity is 980-1090%, while in neutral pH it is significantly higher at 1380-1580%. Hydrogels retain approximately 48% moisture for 8 hours, which is sufficient to ensure the functionality of a hydrogel-type dressing. Rheological analysis showed that the hydrogels exhibit predominantly elastic behavior characteristic of a cross-linked macromolecular network (G’ = 3,450-54,000 Pa). The optimal loading capacity with 5-FU varies depending on pH, loading time, hydrogel composition, and 5-FU concentration, at 200 mg/L of 5-FU is 30% at pH 6 and 29% at pH 5. The release of 5-FU is slow at pH 7.4, gradually reaching 80% or completely within 30 hours, depending on the hydrogel composition. The in vitro release kinetics of 5-FU correlate best with the Korsmeyer-Peppas, Peppas-Sahlin, and Makoid-Banakar kinetic models (R2 > 0.99) and demonstrate that the release of 5-FU is primarily governed by an accelerated mechanism, followed by a diffusion-controlled mechanism. The experimental results demonstrate that hydrogels obtained through irradiation support the loading and release of anticancer drugs and show potential for use as dressings for local cancer treatment.
Abstract grafic:
