مشخصات پژوهش

Objective Carfilzomib (CFZ), a selective proteasome inhibitor, was encapsulated in pH-responsive niosomes to enhance its stability and targeted delivery. Significance This formulation aims to improve the controlled release and therapeutic efficacy of CFZ while minimizing systemic toxicity. Methods Niosomes were prepared via thin-film hydration using ergosterol, CHEMS, Span 60, and Tween 60. The lipid film was hydrated with PBS (pH 7.4) containing CFZ in DMSO at 60 °C, followed by sonication to form unilamellar vesicles. The formulation was characterized for encapsulation efficiency, particle size, drug release, cytotoxicity, and in vivo toxicity. Results Encapsulation efficiency reached 89.82%, with particle size increasing slightly from 323 nm (empty niosomes) to 334 nm (CFZ-loaded). In vitro release was pH-dependent, with 74.39% of CFZ released at pH 5.4 versus 54.55% at pH 7.4. CFZ-loaded niosomes exhibited enhanced cytotoxicity against breast cancer cells (IC₅。 = 0.0415 µM) compared to free CFZ (IC₅。 = 0.0714 µM). A synergistic effect with doxorubicin was observed (combination index <1). In vivo studies showed no significant toxicity at 1 and 2 mg/kg doses. However, 4 mg/kg caused elevations in liver enzymes, BUN, and creatinine, with histopathological signs of liver and kidney damage. Conclusions The CFZ-loaded niosomal system demonstrated optimal size, pH-responsive release, and superior anticancer activity. These findings highlight its potential as an effective carrier for controlled proteasome inhibitor delivery.