A new liposomal nanocarrier for co-delivery of gedunin and p-glycoprotein siRNA to target breast cancer stem cells. Issue 24 (17th December 2022)

• Record Type: Journal Article
• Authors: Rana, Mohan Singh; Ediriweera, Meran Keshawa; Rajagopalan, Umapriyatharshini; Karunaratne, Desiree Nedra; Tennekoon, Kamani Hemamala; Samarakoon, Sameera Ranganath
• Is Part Of: Natural product research. Volume 36:Issue 24(2022)
• Page Start: 6389
• Page End: 6392
• Publication Date: 2022-12-17
• Subjects: Gedunin -- P-glycoprotein -- liposomal nanocarrier -- breast cancer stem cells -- co-delivery; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2022.2032048
• Languages: English
• ISSNs: 1478-6419

Abstract

Abstract: Gedunin is a secondary metabolite found in neem tree. Since the first discovery of this compound, its bio-active properties have been continuously evaluated. However, the low hydrophobicity of gedunin decreases its bioavailability and pharmacokinetic profile. In the present investigation, a new liposomal nanocarrier for co-delivery of gedunin and P-glycoprotein (P-gp) siRNA [siRNA coated liposomal gedunin (Lipo-Ged-siRNA)] was developed to improve the anti-proliferative activity of gedunin. Characteristics of prepared Lipo-Ged-siRNA demonstrated promising effects. Lipo-Ged-siRNA showed greater anti-proliferative effects (IC50 -8.5 µg/mL) followed by pure gedunin (IC50 - 40.2 µg/mL) in breast cancer stem cells (bCSCs). Immunofluorescence analysis demonstrated reduced expression of P-gp following exposure to Lipo-Ged-siRNA. Furthermore, Lipo-Ged-siRNA affected the expression of ABCB1, Cyclin D1, Bax, p53, and surviving genes in bCSCs. Graphical Abstract: UF0001