Saturday, June 30, 2012

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

Now all we need is some drug that actually either helps neurogenesis, angiogenesis, or neuroplasticity and we have the delivery system to get it there. And with magnetic ones we can deliver to specific areas.  Who needs to be talked to to figure out next steps?  God, this is so obvious.
Ranting again, time to let the medical gods sit back and do nothing. WSO - Bo Norrving where are you?
Can any of my Swedish readers see if he can talk to survivors about what he does for the WSO? Does he need help in figuring out where stroke research should go next?
http://www.dovepress.com/articles.php?article_id=10255
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 IC50 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 brain-targeting drug delivery system.

Keywords: chitosan, stearic acid, micelle, blood–brain barrier, brain targeting, in vivo imaging

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