Functionalized Niosomes for Co-Delivery of Curcumin and Imatinib Mesylate to Treat Breast Cancer: In Vitro and In Vivo Investigations

Abstract

Breast cancer is notable for its aggressive mutations, high resistance, and delayed diagnosis. Traditional treatments often cause severe side effects, highlighting the need for targeted therapies. This study developed a targeted delivery system using folic acid and Arginylglycylaspartic acid (RGD)-modified niosomes to deliver hydrophilic imatinib mesylate (IM) and hydrophobic curcumin (C) to treat breast cancer. The formulations were prepared and characaterized for size, zet potential, polydispersity index, % entrapment efficiency, and morphology. Moreover, FTIR (Fourier Transform Infrared) study negated incompatibility. In vitro drug release study was carried out at two different pH. In vitro cytotoxicity (dose dependent and ROS activity) and in vivo bioavailability studies were conducted to generate a proof of concept. The dual drug-loaded niosomal vesicles (R-F-PL64oxNS@IM-C) were designed for effective delivery of IM and C having particle size (< 300 nm) with high zeta potential (- 18 mV). The formulation achieved high entrapment efficiency (>70%) for both drugs with sustained release over 36 h at the explored two pH. In vitro results using MCF- 7 cells revealed significant cell death by R-F-PL64oxNS@IM-C as compared to pure drugs (IM & C) through upregulation and downregulation of proapoptotic and antiapoptotic genes, respectively. In vivo studies showed approximately 1.9- and 5-fold higher biodistribution of C and IM, respectively using targeted niosomal systems as compared to pure drugs. The pharmacokinetic analysis revealed that Cmax and AUC of IM from R-F-PL64oxNS@IM and C from R-F-PL64oxNS@IM-C were significantly higher compared to pure IM and curcumin. Moreover, the Tmax had also increased for both IM (3 h) and C (3 h) using RGD and folic acid guided niosomal formulation suggesting its enhanced retention in systemic circulation leading to more bioavailability as compared to IM (0.5 h) and C (0.5 h). The targeted delivery also led to significant reduction in TNF-α levels, indicating improved therapeutic potential. The developed R-F-PL64oxNS@IM-C shown more precisely killing of breast cancer cell than pure IM and C.

Graphical Abstract