Targeted Nanostructured Lipid Carrier for Brain Delivery of Artemisinin: Design, Preparation, Characterization, Optimization and Cell Toxicity

Abstract

In the present study, a transferrin-conjugated nanostructured lipid carrier (TF-NLCs) for brain delivery of artemisinin (ART) was developed. ART-loaded NLCs (ART-NLCs) were prepared using solvent evaporation method and the impact of various formulation or process variables on the responses were assessed using a Taguchi design. Optimized ART-NLC was then coupled with transferrin as targeting ligand and its in vitro cytotoxicity was investigated against U-87MG brain cancer cell line. As a result, the following values are suggested by the software to prepare the optimized formulation: 20 mg Compritol®, 0.25% Tween 80, 5 mg oleic acid, 2.5 mL dichloromethane and 4 min sonication. Mean particle size (PS), zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE), mean release time (MRT) of adopted formulation were confirmed to be 145 ± 12.5 nm, 24.3 ± 1.5 mV, 0.513 ± 0.021, 82.3 ± 7.3 % and 24.0 ± 1.1 h, respectively. Following conjugation of optimized ART-NLCs with TF, PS and MRT were increased, while ZP, and EE were decreased significantly. TF-ART-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the TF-ART-NLCs could potentially be exploited as a delivery system for anticancer and antimalarial drug ART in brain tumors and malaria.

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

“…Increasing the concentration of LL tends to alter the crystal lattice and increase its imperfections, resulting in a higher EE % than those with more regular crystalline structure. Similarly, increasing the amount of SL, such as Compritol ® 888 ATO, from 10 to 20 mg showed a remarkable increase in EE % of ART [72].…”

Nanomaterials for cancer therapy: current progress and perspectives

“…3 ). Several nanomaterials have been researched for delivery through BBB, including NLCs [ 232 ], liposomes, and AuNPs. A glutathione PEGylated liposome loaded with methotrexate (MTX) was tested in rats and the result showed the nanocarrier improves the brain uptake of MTX [ 233 ].…”

Artemisinins as Anticancer Drugs: Novel Therapeutic Approaches, Molecular Mechanisms, and Clinical Trials

“…Nano-formulations can achieve a drug-targeted distribution and increase the bioavailability of the drug to improve the curative efficacy, which is a key technology in targeted cancer therapy. To improve physicochemical properties of ARTs, researchers have developed ART-based nano-formulations such as liposomes (Gharib et al, 2014;Leto et al, 2016;Gao et al, 2018;Li H. et al, 2019;, nanostructured lipid carriers (Emami et al, 2018), micelles (Nosrati et al, 2019;, nanospheres , nanocapsules (Meng et al, 2014;Tran et al, 2015) and multifunctional nanoparticles (Chen et al, 2014;Li et al, 2014;Wang et al, 2016a;Wang et al, 2016b;Pan et al, 2018) (Table 2). These nano-formulations overcame chemotherapeutic resistance with improved selectivity by targeting tumor cells.…”

“…Based on transferrin overexpression in tumor cells, magnetic nanoliposomes and transferrin-conjugated liposomes were developed to target tumor in vitro and in vivo (Gharib et al, 2014;Leto et al, 2016). Also, ART-loaded transferrin-conjugated nanostructured lipid carriers were developed to increase water solubility, site specificity, selective targeting, efficient penetration, glioma cell distribution and internalization, as well as effective delivery across the bloodbrain barrier with much lower drug concentration, greater therapeutic effect and decreased likelihood of neurotoxicity (Emami et al, 2018).…”