Immobilization and in vitro kinetic controlled release study of doxorubicin from temperature-sensitive mPEG-Ala-Asp polypeptide hydrogel

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The loading of the doxorubicin drug into a new polyethylene glycol-polypeptide based temperature-sensitive hydrogel and the investigation of its properties have been carried out. It was determined that during the immobilization of the drug, equilibrium is reached, and saturation occurs within 3 hours in a solution with an initial antibiotic concentration of approximately 4.8 mg/mL. Currently, 84-87 % of the drug is adsorbed, meaning that 100 mg of gel drug capacity was 405.8 mg/gr. The samples were kept in different pH solutions (pH = 2, 7.4, and 8.6) at 37 °C, and the release of doxorubicin was kinetically studied over intervals ranging from 0-300 minutes. It was determined that changes in the ionic strength of the solution lead to a change in the polarity degree of the chemical bond between the hydrogel and doxorubicin. The results of doxorubicin release from the gel were tested against various kinetic models, including zero-order, first-order, Higuchi square root law, Korsmeyer-Peppas, and Hixson-Crowell square root models. When applying the kinetic results of doxorubicin release from the gel to the Korsmeyer-Peppas model, in acidic and neutral mediums, the value of n > 1, which is attributed to the breaking of protein segments in the terminal groups of the matrix. This makes the creation of thin-coated drug formulations from the matrix more advantageous. In an alkaline medium, however, n < 1, indicating that the release follows a non-Fickian mechanism, characterized by both diffusion and erosion. To ensure release in an alkaline medium, it is more appropriate to prepare cylindrical, spherical, or film-type drug forms from the PEG-Ala-Asp gel. Also, since the gel formation time can be adjusted, such systems can be recommended as analogues of injectable thermosetting insulation composites for the oil and gas industry. Keywords: temperature sensitive; polyethyenglycol; polypeptide gel; release kinetic; doxorubicine.