Laser thrombolysis and in vitro release kinetics of tPA encapsulated in chitosan polysulfate-coated nanoliposome

Abstract

A major challenge in managing coronary artery disease is to find an effective thrombolytic therapy with minimal side effects. Laser thrombolysis is a practical procedure to remove the thrombus from inside blocked arteries, although it can cause embolism and re-occlusion of the vessel. The present study aimed to design a liposome drug delivery system for the controlled release of tissue plasminogen activator (tPA) and delivery of drug system into the thrombus by Nd:YAG laser at a wavelength of 532 nm for the treatment of arterial occlusive diseases. In this study, tPA encapsulated into the chitosan polysulfate-coated liposome (Lip/PSCS-tPA) was fabricated by a thin-film hydration technique. The particle size of Lip/tPA and Lip/PSCS-tPA was 88 and 100 nm, respectively. The release rate of tPA from Lip/PSCS-tPA was measured to be 35 % and 66 % after 24 h and 72 h, respectively. Thrombolysis through the delivery of Lip/PSCS-tPA into the thrombus during the laser irradiation was higher compared to irradiated thrombus without the nanoliposomes. The expression of IL-10 and TNF-α genes was studied by RT-PCR. The level of TNF-α for Lip/PSCS-tPA was lower than that of tPA, which can lead to improved cardiac function. Also, in this study, the thrombus dissolution process was studied using a rat model. After 4 h, the thrombus area in the femoral vein was significantly lower for groups treated with Lip/PSCS-tPA (5 %) compared to the groups treated with tPA alone (45 %). Thus, according to our results, the combination of Lip/PSCS-tPA and laser thrombolysis can be introduced as an appropriate technique for accelerating thrombolysis.

Keywords: Chitosan polysulfate; Coronary artery disease; Nd:YAG laser thrombolysis; Thrombus dissolution; Tissue plasminogen activator.