Physicochemical Characterization, Drug Release, Stability, and Cytotoxicity of Cross-Linked Curdlan-Based Nanosponges for α-Amyrin and Higenamine Delivery

Abstract

Objectives: Michigan cancer foundation-7 (MCF-7) breast-cancer cells are recognized for their resilience against conventional chemotherapy drugs and apoptosis-triggering agents. Nanosponges (NSs) have emerged as promising drug-delivery systems in cancer therapy because of their ability to encapsulate and deliver therapeutic agents efficiently. The aim of this study was to establish the combined beneficial anticancer impacts of NSs alpha-amyrin (AMY) and higenamine (HGN) on MCF-7 breast-cancer cells. Materials and Methods: NSs were developed using a solvent-evaporation technique that used dichloromethane as the solvent and curdlan as the polymer. A comprehensive randomized 3² factorial design was employed to vary curdlan content (X1) and stirring rate (revolutions per minute, X2) and to investigate their influence on particle size (Y1) and entrapment efficiency (EE, Y2). The optimized formulation then underwent in-vitro investigations, encompassing apoptosis and cell-cycle studies with the MCF-7 breast-cancer cell line. Results: The prepared NSs (F1-F9) exhibited optimal physical and chemical characteristics. Optimization produced formulation F10, which achieved a particle size of 280.9 nm and an EE of 63.00%. The model was established for all dependent variables, such as particle size and EE, at a significance level of p<0.05. In vitro studies of the prepared NSs demonstrated promising anticancer activity. The AMY + HGN combination showed synergistic effects versus AMY alone, significantly influencing the MCF-7 cell cycle, producing G1-phase arrest, and reducing cell propagation by flow-cytometry analysis. Conclusion: The synergistic anticancer activity observed with AMY-and HGN-loaded NSs-combined with their sustained-release properties and cell-cycle modulation in MCF-7 cells-underscores the promise of this formulation as an effective cancer-treatment approach.