Enhanced Intracellular Delivery of Curcumin by Chitosan-Lipoic Acid as Reduction-Responsive Nanoparticles

Somayeh Rezaei; Soheila Kashanian; Yadollah Bahrami; Hossein Zhaleh; Luis J Cruz

doi:10.2174/1389201021999200727153513

Enhanced Intracellular Delivery of Curcumin by Chitosan-Lipoic Acid as Reduction-Responsive Nanoparticles

Curr Pharm Biotechnol. 2021;22(5):622-635. doi: 10.2174/1389201021999200727153513.

Authors

Somayeh Rezaei¹, Soheila Kashanian², Yadollah Bahrami², Hossein Zhaleh³, Luis J Cruz⁴

Affiliations

¹ Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran.
² Department of Medical Biotechnology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran.
³ Substance Abuse Prevention Research Center, Kermanshah University of Medical Science, Kermanshah, Iran.
⁴ Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.

PMID: 32720599
DOI: 10.2174/1389201021999200727153513

Abstract

Aims: Enhancement of anti-tumor activity of the chemotherapeutic agent CUR by redoxsensitive nanoparticle to get a deeper insight into cancer therapy.

Background: Tumor targetability and stimulus are widely used to study the delivery of drugs for cancer diagnosis and treatment because poor cellular uptake and inadequate intracellular drug release lead to inefficient delivery of anticancer agents to tumor tissue.

Objective: Studies distinguishing between tumor and normal tissues or redox-sensitive systems using glutathione (GSH) as a significant signal.

Methods: In this study, we designed Chitosan-Lipoic acid Nanoparticles (CS-LANPs) to improve drug delivery for breast cancer treatment by efficient delivery of Curcumin (CUR). The properties of blank CS-LANPs were studied in detail. The size and the Polydispersity Index (PDI) of the CS-LANPs were optimized.

Results: The results indicate the mean size and PDI of the blank CS-LANPs were around 249 nm and 0.125, respectively. However, the Drug Loading (DL) and Encapsulation Efficiency (EE) of the CSLANPs were estimated to be about 18.22% and 99.80%, respectively. Compared to non-reductive conditions, the size of reduction-sensitive CS-LANPs increased significantly under reductive conditions. Therefore, the drug release of CS-LANPs in the presence of glutathione was much faster than that of non-GSH conditions .Moreover, the antitumor effect of CS-LANPs on MCF-7 cells was determined in vitro by MTT assay, cell cytotoxicity, Caspase-3 Assay, detection of mitochondrial membrane potential and quantification of apoptosis incidence.

Conclusion: CS-LANPs showed a remarkably increased accumulation in tumor cells and had a better tumor inhibitory activity in vitro. CS-LANPs could successfully deliver drugs to cancer cells and revealed better efficiency than free CUR.

Keywords: Curcumin; MCF-7 cells; chitosan; efficient delivery.; glutathione; lipoic acid; reduction-responsive nanoparticles.

MeSH terms

Antineoplastic Agents, Phytogenic / administration & dosage*
Antineoplastic Agents, Phytogenic / chemistry
Capsules
Caspase 3 / analysis
Caspase 3 / metabolism
Chitosan / chemistry*
Curcumin / administration & dosage*
Curcumin / chemistry
Drug Carriers
Drug Delivery Systems
Drug Liberation
Drug Screening Assays, Antitumor
Female
Humans
MCF-7 Cells
Nanoparticles
Oxidation-Reduction
Thioctic Acid / chemistry*

Substances

Antineoplastic Agents, Phytogenic
Capsules
Drug Carriers
Thioctic Acid
Chitosan
CASP3 protein, human
Caspase 3
Curcumin