Preparation and Evaluation of Diosmin-Loaded Diphenylcarbonate-Cross-Linked Cyclodextrin Nanosponges for Breast Cancer Therapy
Md. Khalid Anwer, Mohammed Muqtader Ahmed, Mohammed F. Aldawsari, Muzaffar Iqbal, Vinay Kumar
Abstract
In the current study, diosmin (DSM)-loaded beta-cyclodextrin (β-CD)-based nanosponges (NSPs) using diphenylcarbonate (DPC) as a cross-linker were prepared. Four different DSM-loaded NSPs (D-NSP1-NSP4) were developed by varying the molar ratio of β-CD: DCP (1:15-1:6). Based on preliminary evaluations, NSPs (D-NSP3) were optimized for size (412 ± 6.1 nm), polydispersity index (PDI) (0.259), zeta potential (ZP) (-10.8 ± 4.3 mV), and drug loading (DL) (88.7 ± 8.5%), and were further evaluated by in vitro release, scanning electron microscopy (SEM), and in vitro antioxidant studies. The NSPs (D-NSP3) exhibited improved free radical scavenging activity (85.58% at 100 g/mL) compared to pure DSM. Dissolution efficiency (%DE) was enhanced to 71.50% (D-NSP3) from plain DSM (58.59%). The D-NSP3 formulation followed the Korsmeyer-Peppas kinetic model and had an n value of 0.529 indicating a non-Fickian and controlled release by diffusion and relaxation. The D-NSP3 showed cytotoxic activity against MCF-7 breast cancer, as evidenced by caspase 3, 9, and p53 activities. According to the findings, DSM-loaded NSPs might be a promising therapy option for breast cancer.