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

Abstract

Aim: Enhancement of anti-tumor activity of the chemotherapeutic agent CUR by redox-sensitive nanoparticle to get a deeper in-sight 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 is 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 treatmentby 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 CS-LANPs were estimated to be about 18.22% and 99.80%, respectively. Com-pared 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 ef-fect 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.

Chitosan–Hyaluronic Acid Nanoparticles for Active Targeting in Cancer Therapy

“…Ligands will be conjugated on the surface of nanoparticles, resulting in increased cellular absorption via endocytosis-mediated receptors, increasing drug accumulation in cancer cells. The basis for this process is the interaction between ligands conjugated on the surface of nanoparticles and cell surface receptors or antigens on the surface of cancer cells [20]. One of the ligands that is widely used to target drugs is hyaluronic acid [41][42][43][44].…”

“…This method relies on the interaction between ligands on the surface of nanoparticles and cell surface receptors of cancer cells [19]. Hyaluronic acid (HA) is a polysaccharide ligand used chiefly for active targeting systems because of its high selectivity and affinity to CD44 receptors highly expressed in different tumor cells [18,20].…”

Polymer-Based Drug Delivery Systems for Cancer Therapeutics

“…[192] Chitosan-lipoic acid reduction-responsive (CS-LANPs) Curcumin Self-assembly Increased tumor accumulation with a better tumor inhibitory activity in vitro. [193] 3.2.5. Other Stimuli-Responsive (Thermo-, Hypoxia-, and Enzyme-Responsive) Polymers…”