Targeted nanostructured lipid carrier containing galangin as a promising adjuvant for improving cytotoxic effects of chemotherapeutic agents
- 15 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie
- Vol. 394 (12), 2353-2362
- https://doi.org/10.1007/s00210-021-02152-9
Abstract
Resistance to chemotherapeutic drugs is the main limitation of cancer therapy. The combination use of chemotherapeutic agents and galangin (a naturally active flavonoid) amplifies the effectiveness of cancer treatment. This study aimed to prepare arginyl-glycyl-aspartic acid (RGD) containing nanostructured lipid carrier (NLC-RGD) to improve the bioavailability of galangin and explore its ability in improving the cytotoxic effects of doxorubicin (DOX). Galangin-loaded NLC-RGD was prepared by hot homogenization method and characterized by diverse techniques. Then, cytotoxicity, uptake, and apoptosis induction potential of prepared nanoparticles beside the DOX were evaluated on A549 lung cancer cells. Finally, the expression level of some ABC transporter genes was evaluated in galangin-loaded NLC-RGD-treated cells. Nanoparticles with appropriate characteristics of the delivery system (size: 120 nm, polydispersity index: 0.23, spherical morphology, and loading capacity: 59.3 mg/g) were prepared. Uptake experiments revealed that NLC-RGD promotes the accumulation of galangin into cancerous cells by integrin-mediated endocytosis. Results also showed higher cytotoxicity and apoptotic effects of DOX + galangin-loaded NLC-RGD in comparison to DOX + galangin. Gene expression analysis demonstrated that galangin-loaded NLC-RGD downregulates ABCB1, ABCC1, and ABCC2 more efficiently than galangin. These findings indicated that delivery of galangin by NLC-RGD makes it an effective adjuvant to increase the efficacy of chemotherapeutic agents in cancer treatment.Keywords
Funding Information
- Baqiyatallah University of Medical Sciences (98000453)
This publication has 37 references indexed in Scilit:
- Physical Chemistry of Nanomedicine: Understanding the Complex Behaviors of Nanoparticles in VivoAnnual Review of Physical Chemistry, 2015
- Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH effluxBiochemical Pharmacology, 2014
- The effects of flavonoids on the ABC transporters: consequences for the pharmacokinetics of substrate drugsExpert Opinion on Drug Metabolism & Toxicology, 2012
- Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrinNanotechnology, 2012
- Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathwayJournal of Asian Natural Products Research, 2012
- Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersionColloids and Surfaces B: Biointerfaces, 2011
- First-Pass Metabolism via UDP-Glucuronosyltransferase: a Barrier to Oral Bioavailability of PhenolicsJournal of Pharmaceutical Sciences, 2011
- Galangin Suppresses the Proliferation of β-Catenin Response Transcription-Positive Cancer Cells by Promoting Adenomatous Polyposis Coli/Axin/Glycogen Synthase Kinase-3β-Independent β-Catenin DegradationMolecular Pharmacology, 2011
- Integrin V 6 is a high-affinity receptor for coxsackievirus A9Journal of General Virology, 2009
- Modulation of adriamycin® accumulation and efflux by flavonoids in HCT-15 colon cells: Activation of P-glycoprotein as a putative mechanismBiochemical Pharmacology, 1994