Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle

BACKGROUND AND METHODS: Silica-coated magnetic nanoparticle (SiO(2)-MNP) prepared by the sol-gel method was studied as a nanocarrier for targeted delivery of tissue plasminogen activator (tPA). The nanocarrier consists of a superparamagnetic iron oxide core and an SiO(2) shell and is characterized b...

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Detalles Bibliográficos
Autores principales: Chen, Jyh-Ping, Yang, Pei-Ching, Ma, Yunn-Hwa, Tu, Su-Ju, Lu, Yu-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Original Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463402/
https://www.ncbi.nlm.nih.gov/pubmed/23055726
http://dx.doi.org/10.2147/IJN.S36197
Descripción
Sumario:BACKGROUND AND METHODS: Silica-coated magnetic nanoparticle (SiO(2)-MNP) prepared by the sol-gel method was studied as a nanocarrier for targeted delivery of tissue plasminogen activator (tPA). The nanocarrier consists of a superparamagnetic iron oxide core and an SiO(2) shell and is characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, superconducting quantum interference device, and thermogravimetric analysis. An amine-terminated surface silanizing agent (3-aminopropyltrimethoxysilane) was used to functionalize the SiO(2) surface, which provides abundant –NH(2) functional groups for conjugating with tPA. RESULTS: The optimum drug loading is reached when 0.5 mg/mL tPA is conjugated with 5 mg SiO(2)-MNP where 94% tPA is attached to the carrier with 86% retention of amidolytic activity and full retention of fibrinolytic activity. In vitro biocompatibility determined by lactate dehydrogenase release and cell proliferation indicated that SiO(2)-MNP does not elicit cytotoxicity. Hematological analysis of blood samples withdrawn from mice after venous administration indicates that tPA-conjugated SiO(2)-MNP (SiO(2)-MNP-tPA) did not alter blood component concentrations. After conjugating to SiO(2)-MNP, tPA showed enhanced storage stability in buffer and operation stability in whole blood up to 9.5 and 2.8-fold, respectively. Effective thrombolysis with SiO(2)-MNP-tPA under magnetic guidance is demonstrated in an ex vivo thrombolysis model where 34% and 40% reductions in blood clot lysis time were observed compared with runs without magnetic targeting and with free tPA, respectively, using the same drug dosage. Enhanced penetration of SiO(2)-MNP-tPA into blood clots under magnetic guidance was confirmed from microcomputed tomography analysis. CONCLUSION: Biocompatible SiO(2)-MNP developed in this study will be useful as a magnetic targeting drug carrier to improve clinical thrombolytic therapy.

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