Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system
Yi-Ting Xie, Yong-Zhong Du, Hong Yuan, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaPurpose: Therapy for central nervous system disease is mainly restricted by the blood–brain barrier. A drug-delivery system is an effective approach to overcome thi...
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Dove Medical Press
2012
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oai:doaj.org-article:1364b0211f594332ad6ea8331fe2d7bb2021-12-02T03:19:10ZBrain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system1176-91141178-2013https://doaj.org/article/1364b0211f594332ad6ea8331fe2d7bb2012-06-01T00:00:00Zhttp://www.dovepress.com/brain-targeting-study-of-stearic-acidndashgrafted-chitosan-micelle-dru-a10255https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yi-Ting Xie, Yong-Zhong Du, Hong Yuan, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaPurpose: 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 imagingXie YTDu YZYuan HHu FQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3235-3244 (2012) |
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Medicine (General) R5-920 Xie YT Du YZ Yuan H Hu FQ Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
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Yi-Ting Xie, Yong-Zhong Du, Hong Yuan, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaPurpose: 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 |
| format |
article |
| author |
Xie YT Du YZ Yuan H Hu FQ |
| author_facet |
Xie YT Du YZ Yuan H Hu FQ |
| author_sort |
Xie YT |
| title |
Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| title_short |
Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| title_full |
Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| title_fullStr |
Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| title_full_unstemmed |
Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| title_sort |
brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/1364b0211f594332ad6ea8331fe2d7bb |
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