Enhanced thrombolytic therapy for stroke: Targeted delivery of urokinase with magnetic nanoparticles

To achieve target thrombolysis, we will further optimize our system in the second year. Preparation of both PAA-MNP-urokinase or chotosan-MNP-urokinase can be further optimized to increase the enzyme activity per MNP in vitro (Aim 1a), which appears to be essential before testing target thrombolysis in vivo (Aim 2). In addition, other formulation will be tested to determine the feasibility (Aim 1b or 1c). Characterization of MNP-urokinase will be conducted to determine the optimized conditions (Aim 1d). Mathematic modeling and computer simulation for the intravascular fluid mechanics of MNP-urokinase under the influence of external magnetic influence will be conducted (Aim 2a), followed by quantitation of intravascular retention of MNP-urokinase under magnetic guidance (Aim 2b). If significant MNP retention can be observed, we may be able to use the iliac embolic model established in the first year to determine whether MNP-urokinase may exert a target thrombolysis effect under magnetic targeting. In the 1st year study, we have demonstrated that ultrasound may enhance MNP suspension in vitro, we will further determine whether ultrasound may preserve enzyme activity while enhancing dispersion (Aim 3a & 3b). We will employ both ultrasound and magnetic guidance to determine the efficacy and MNP biodistribution in the rat iliac embolic model and rat embolic stroke mode. (Aim 4c). In conclusion, we expect to further optimize the drug composite to be tested in the rat embolic model during the second funding year.

Project ID:PG10001-0106
External Project ID:NHRI-EX100-9937EI