Magnetically controlled release of recombinant tissue plasminogen activator from chitosan nanocomposites for targeted thrombolysis. Issue 15 (24th March 2016)

• Record Type: Journal Article
• Authors: Chen, Jyh-Ping; Liu, Chih-Hsin; Hsu, Hao-Lung; Wu, Tony; Lu, Yu-Jen; Ma, Yunn-Hwa
• Is Part Of: Journal of materials chemistry. Volume 4:Issue 15(2016)
• Page Start: 2578
• Page End: 2590
• Publication Date: 2016-03-24
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c5tb02579f
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : Targeted delivery and triggered release of rtPA-encapsulated magnetic chitosan nanoparticles with the guidance of a magnet could be used for remote-controlled thrombolysis therapy. Abstract : Ionic cross-linking of water-soluble chitosan with sodium tripolyphosphate in the presence of recombinant tissue plasminogen activator (rtPA) and magnetite (Fe3 O4 ) nanoparticles could produce rtPA-encapsulated magnetic chitosan nanoparticles (MCNPs–rtPA). MCNPs do not elicit cytotoxicity and hemolysis in vitro . MCNPs–rtPA showed a negligible release of the rtPA protein when stored in phosphate buffer for 28 days. In contrast, the burst release of rtPA from MCNPs–rtPA was found in the serum with 60% of the original activity released in 30 min. The drug release into the serum is also magnet-sensitive; the release could be turned down with a magnetic field when MCNPs–rtPA was pelleted and reversibly turned on after removing the magnetic field when MCNPs–rtPA was dispersed. An in vitro thrombolytic study by thromboelastometry indicated a controlled release of rtPA from MCNPs–rtPA. In a rat embolic model where a preformed blood clot lodged in the left iliac artery upstream of the pudic epigastric branch, MCNPs–rtPA (0.2 mg kg −1 rtPA) was administered and guided magnetically to the clot, followed by mobile magnetic guidance for 60 min. Iliac blood flow increased immediately in response to the treatment, and reached a stable level ∼50 min after drug administration and the hind limb perfusion rate was restored from 53% to 75% of the basal level. Effective thrombolysis was therefore successfully demonstrated at an rtPA dose equivalent to 20% of the regular dose when the MCNPs–rtPA pellet was magnet-guided to the blood clot, followed by a triggered release of rtPA when switched to mobile magnetic guidance.