期刊
CARBOHYDRATE POLYMERS
卷 84, 期 1, 页码 364-372出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2010.11.052
关键词
Magnetic nanoparticles; Chitosan; Drug delivery; Thrombolysis; Tissue plasminogen activator
资金
- National Science Council [98-2120-M-182-001]
- National Health Research Institute [NHRI-EX99-9937EI]
- Chang Gung Memorial Hospital [CMRPD250023]
In this study, we examine the preparation of chitosan-coated magnetic nanoparticle (MNP) (chitosan-MNP) and the feasibility of using tissue plasminogen activator (tPA) covalently bound to chitosan-MNP surface (chitosan-MNP-tPA) for magnetic targeted delivery of the thrombolytic drug. The physicochemical properties of chitosan-MNP prepared with increasing chitosan/MNP ratios were characterized in detail. The optimum drug loading is reached when 0.5 mg tPA is conjugated with 5 mg chitosan-MNP where 95% drug is attached to the carrier with full retention of its thrombolytic activity. Under magnetic guidance, chitosan-MNP-tPA can reduce the blood clot lysis time by 58% compared with runs without magnetic targeting or by 53% compared with free tPA using the same drug dosage. Effective thrombolysis in response to chitosan-MNP-tPA under magnetic guidance is also demonstrated in a rat embolic model where one-fifth of the dose of tPA may exert similar thrombolytic efficacy of the drug. (C) 2010 Elsevier Ltd. All rights reserved.
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