Targeted nanostructured lipid carrier containing galangin as a promising adjuvant for improving cytotoxic effects of chemotherapeutic agents.

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.

• Authors: Hamed Hajipour, Mohammad Nouri, Marjan Ghorbani, Ali Bahramifar, Reza Zolfaghari Emameh, Ramezan Ali Taheri
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 394 Issue 12 Pg. 2353-2362 (12 2021) ISSN: 1432-1912 [Electronic] Germany
• PMID: 34522984 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Flavonoids
• Lipids
• Oligopeptides
• galangin
• arginyl-glycyl-aspartic acid
• Doxorubicin

Topics

• A549 Cells
• Antibiotics, Antineoplastic (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Doxorubicin (administration & dosage, pharmacology)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Resistance, Neoplasm
• Flavonoids (administration & dosage, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lipids (chemistry)
• Lung Neoplasms (drug therapy)
• Nanoparticles
• Oligopeptides (chemistry)
• Particle Size