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Research Article: Coencapsulation of doxorubicin and curcumin in liposomes modified with folic acid for reversal of drug resistance in glioma

Date Published: 2026-06-17

Abstract:
Multidrug resistance (MDR) critically limits doxorubicin (Dox) efficacy in glioma. To overcome this, we constructed a folic acid receptor (FAR)-targeted liposomal system for codelivering Dox and curcumin (Cur). Dox/Cur-Lip@FA was prepared using the film hydration-sonication method. The physicochemical properties (size, zeta potential, encapsulation efficiency, and drug release) were characterized. The studies assessed P-gp modulation and cellular uptake in Dox-resistant C6 cells, as well as in vivo efficacy in xenograft models. The FA ligand enabled selective tumor targeting by binding to overexpressed FAR, while Cur enhanced Dox efficacy by downregulating P-gp-mediated drug efflux. Dox/Cur-Lip@FA exhibited a uniform size of 112.5 ± 3.8 nm, a zeta potential of -7.85 ± 0.62 mV, high dual-drug EE% (Dox: 91.32 ± 3.95%; Cur: 90.87 ± 4.21%), and sustained release kinetics. In vitro , targeted liposomes achieved 3.56-fold higher cellular uptake in Dox-res-C6 cells compared to non-targeted formulations. In an in vitro BBB model, FA modification significantly enhanced transendothelial transport, suggesting potential for brain delivery. In vivo , Dox/Cur-Lip@FA induced a 71.19% reduction in tumor volume, significantly outperforming free drugs and non-targeted liposomes. Mechanistic analysis confirmed that Cur effectively suppressed P-gp expression, thereby restoring Dox sensitivity. This FA-functionalized codelivery system combines active targeting with MDR reversal, showing improved cellular uptake in vitro and antitumor efficacy in subcutaneous xenografts, with potential for BBB penetration as suggested by in vitro models.

Introduction:
Multidrug resistance (MDR) critically limits doxorubicin (Dox) efficacy in glioma. To overcome this, we constructed a folic acid receptor (FAR)-targeted liposomal system for codelivering Dox and curcumin (Cur).

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