Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Abstract

Purpose: Therapy for central nervous system disease is mainly restricted by the blood-brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied. Methods: Stearic acid-grafted chitosan (CS-SA) was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX), as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells. Results:The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC 50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX ⋅ HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood-brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour. Meanwhile, free DOX ⋅ HCl was not detected in brain. In other major tissues, DOX-loaded micelles were mainly distributed into lung, liver, and spleen, with a reduction of DOX accumulation in heart. Conclusion: The CS-SA micelles were able to be used as a promising carrier for a braintargeting drug delivery system.

Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery

“…Zeta potential was calculated from electrophoretic mobility using the The morphology of the nanoparticles was determined using transmission electron microscopy (TEM; Philips/FEI CM120 Bio Twin, FEI Netherlands). Samples were placed on copper grids for viewing and excess droplets were wicked away with filter paper [32]. After 2 min, a drop of 1% phosphotungstic acid was placed onto the copper grid for negative staining.…”

Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways

“…Primary amines in chitosan could also play an essential role protective effect during stroke [15]. Moreover, the chitosan-based nanoparticles have been already exploited as delivery system for brain targeting [16][17][18]. They can open tight junctions between intestinal epithelial cell and facilitate paracellular transport of drugs transiently [19].…”

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

“…The reaction begins when EDC reacts to form the O-acylisourea intermediate product easily displaced by the amino groups in the chitosan to create the new covalent bond. EDC reaction can be performed previously, during, or after the nanoparticle synthesis [68][69][70]. Some methods apply the carboxyl activation with regents like dimethyl aminopyridine and 1,4-dioxane triethylamine, then in a second step, EDC is useful as a catalyst to achieve amide bond [71].…”