Despite the diversity of available formulations for relieving topical symptoms of chronic skin diseases, inflammation, and hypergranulation tissue resulting from burn wounds, their efficacy is limited by side effects, application inconveniences, including the oiliness of the formulations, and the need for frequent application, which can affect patient compliance. Therefore, research has been carried out on freeze-dried hydrogel delivery systems of hydrocortisone, to evaluate their physicochemical (gel fraction, swelling ratio, pH and conductivity measurements), structural (FTIR), and morphological (SEM) properties, as well as their cytotoxicity (MTT tests). The gel fraction of freeze-dried hydrogel biomaterials (M-TH25 and M-TH50) reached 64% ± 0.3 and 63% ± 1.7, respectively, slightly higher than for the reference matrix (M) (61 ± 0.8). The swelling ratio (pH = 7.4) was in the range of 212–253% and 184–222%, respectively, comparable to the reference sample (208–277%). The incorporation of a thermosensitive polymeric nanocarriers (poly-N-isopropylacrylamide copolymers) containing hydrocortisone in the quantitative range 25–50 mg did not significantly change the overall morphology of the biomaterials. Both M and M-TH25 samples exhibit non-cytotoxicity towards mouse fibroblast cells BALB/3T3 (93% ± 10; 100% ± 8) and L929 (114% ± 8; 72% ± 10) cells with an observable variation in response for the M-TH25 sample, likely due to differences in cell behaviour and surface area. Importantly, M-TH50 sample shows cytotoxic effects (40% ± 5; 59% ± 4) mainly resulting from an excessively high concentration of the incorporated active substance. Further studies are planned (including on the release profile and kinetics of hydrocortisone and the assessment of the therapeutic effect), which may help to select an appropriate concentration of drug in the quantitative range 25-40 mg.
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