Development and Evaluation of Artesunate-Loaded Chitosan-Coated Lipid Nanocapsule as a Potential Drug Delivery System Against Breast Cancer

Abstract

Artesunate (ART)--a well-known hydrophobic anti-malarial agent was incorporated in a polymer-lipid hybrid nanocolloidal system for anti-cancer therapeutic. The lipid negatively charged nanoemulsion was formulated by modified hot homogenization method then covered with positively charged chitosan via electrostatic interaction to obtain chitosan-coated lipid nanocapsule (ART-CLN). Physical properties of the system were characterized in terms of size, charge, morphology, drug loading capacity, and physical state. In addition, anti-cancer activities were confirmed by conducting MTT assay for ART and ART-CLN on different cancer cell lines. Obtained ART-CLN after coating chitosan revealed positive charge (13.2 ± 0.87 mV), small particle size (160.9 ± 3.5 nm), and spherical shape. High drug entrapment efficiency (95.49 ± 1.13%) and sustained release pattern were observed. Moreover, the good cellular uptake was recorded by flow cytometry as well as confocal image. Finally, ART-CLN exhibited stronger anti-cancer activity than free ART on breast cancer cell lines (MCF-7, MDA-MB-231). These results suggested that by loading ART into lipid core of polymer-lipid hybrid carrier, the activity and physical stability of ART can be significantly increased for cancer chemotherapy.

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

“…In principle, drug encapsulation can improve specificity and bioavailability as well as alter pharmacokinetic properties of the drug. 135 The recent years have seen a remarkable surge of studies exploring various approaches in nanomedicine, ranging from liposomal delivery, [136][137][138][139][140][141] encapsulation with other drugs or biomolecules including transferrin, [142][143][144][145] encapsulation with specific properties such as magnetic or pH-responsive liposomes, [143][144][145][146] novel metal based nanostructures, 146,147 solid lipid nanoparticles (SLNs), and niosomes. 148 In general, these studies have consistently reported positive results with significant enhancements to efficacy and improved selectivity.…”

Mechanisms of the pH- and Oxygen-Dependent Oxidation Activities of Artesunate

“…5) Although the mechanism of action of these artemisinin derivatives on malarial parasites has not been elucidated, the injury caused by malarial parasites is presumed to be caused by free radicals generated by a reaction with heme produced in malarial phagocyte cells. [6][7][8][9][10] Recently, it has been reported that artemisinin derivatives also exert anti-tumor activity in cancer cells, [11][12][13][14][15][16][17][18] which has attracted attention for use in anti-cancer drugs. The reported mechanisms that might explain the antitumor activity of artemisinin derivatives include induction of apoptosis through reactive oxygen species (ROS) generation, 11) angiogenesis inhibitory effects, 19) inhibition of hypoxia-inducible factor-1α (HIF-1α) activation by ROS generation, 20) and direct DNA injury.…”

Progress in nano-drug delivery of artemisinin and its derivatives: towards to use in immunomodulatory approaches

“…Tran and coworkers employed chitosan-coated lipid nanocapsules with AS aiming drug sustained release profile and enhanced cellular uptake increasing cytotoxicity. The results showed evident antitumor activity against breast cancer lines (MCF-7, MDA-MB-231), compared with free AS [24].…”