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Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
11351 734 2008 10 PDF Available
Title
Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles
Abstract

Accelerating thrombolysis using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles by pressure-driven permeation have been demonstrated in vitro and in vivo in animal models. However, designing and delivering PA-encapsulated nanoparticles (NPs) to enhance thrombolysis by applying electrostatic forces or ligand–receptor interactions between the NPs and blood clots has not been proposed. Therefore, without a pressure-driving factor, tissue-plasminogen activator (t-PA) encapsulated in PLGA NPs with chitosan (CS) and CS-GRGD coating and their thrombolysis capabilities in a blood clot-occluded tube model were evaluated by determining clot lysis times and the masses of the digested clots. The characteristics and release profiles of t-PA-encapsulated PLGA, PLGA/CS and PLGA/CS-GRGD NPs are determined by FT-IR, a laser particle/zeta potential analyzer and HPLC. Additionally, the permeation capacities of the NPs into flat blood clots were examined. For example, the mean particle sizes and encapsulation efficacies of t-PA for the NPs are in the ranges 260–320 nm and 65.5–70.5%, respectively. The results reveal that the NPs for the shortest clot lysis time and the highest weight percentages of digested clot are PLGA/CS (20.7±0.7 min) and PLGA/CS-GRGD (25.7±1.3 wt%), respectively. Compared with t-PA solution, the NPs can significantly shorten clot lysis times in the following order: PLGA/CS NPs (38.8±1.5%) >PLGA/CS-GRGD NPs (16.3±1.0%) >PLGA NPs (7.7±1.2%). Compared with t-PA solution, the NPs significantly increase the weight of digested clots in the order, PLGA/CS-GRGD (40.9±1.5%) >PLGA/CS (27.8±1.2%) >PLGA (8.6±0.6%). The highest release rate of t-PA in the fast release phase and the highest permeability into intra-clots of PLGA/CS and PLGA/CS-GRGD NPs, respectively, correspond to the shortest clot lysis time and the largest increase in weight of the digested clots among the NP system. In conclusion, the NPs designed based on new concepts significantly accelerate thrombolysis in vitro in this model, and may be useful in clinical study.

Keywords
t-PA-encapsulated NPs; Chitosan; Chitosan-GRGD; Clot-occluded model; Thrombolysis
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Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 2, January 2008, Pages 228–237
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us