Akademik Veri Yönetim Sistemi
Journal of Drug Delivery Science and Technology, cilt.111, 2025 (SCI-Expanded)
Rheumatoid arthritis is a chronic disease that causes inflammation in various tissues. Glucocorticoids are used in its treatment at high doses at frequent intervals, causing side effects that reduce the life standard of the patients. In this study, three types of nanoparticles that include chitosan (CS) and/or sodium tripolyphosphate (TPP) and/or hyaluronic acid (HA) were developed by choosing hydrocortisone (HC) as a representative model drug of glucocorticoids. Formulation optimization studies were carried out by Box-Behnken experimental design, CS:TPP, CS:HA and CS:TPP:HA nanoparticles were prepared by using chitosan solution at pH 3. CS:TPP and CS:HA ratios were chosen as 2:1 and 0.5:1, stirring time and stirring rate were adjusted to 35 min and 1000 rpm, respectively. The particle sizes of CS:TPP, CS:HA and CS:TPP:HA formulations were found as 320.9 ± 25.9, 204.4 ± 10.6, 302.5 ± 28.2 nm and zeta potentials as 28.5 ± 0.611, −14.6 ± 2.01, −17.7 ± 0.305 mV, respectively. As a result of in vitro release studies, CS:TPP:HA formulation released the least HC at the end of 24 h at pH 7.4, which represents blood and healthy synovial fluid pH, higher HC release was provided in acidic pH representing inflamed tissue environment. The particle size of CS:TPP:HA nanoparticles didn't change significantly at pH 7.4, during in vitro stability studies. 6-month-stability study results showed that CS:TPP:HA was stable at 4 °C and 25° ± 60 % relative humidity, and cytotoxicity tests showed that it was noncytotoxic. To conclude, CS:TPP:HA nanoparticles are the most promising formulation among the three different nanoparticles that were suggested for rheumatoid arthritis treatment as a pH sensitive drug carrier.