On-Chip Preparation of Streptokinase Entrapped in Chitosan Nanoparticles Used in Thrombolytic Therapy Potentially

The objective of this work was to prepare the streptokinase (SK) entrapped in chitosan nanoparticles (CS NPs) using bulk mixing (BM) and microfluidic (MF) techniques. The physicochemical properties of the samples were characterized by means of scanning electron microscopy and dynamic light scattering analysis for optimizing CS and SK solution concentrations as well as pH values. The obtained results showed that CS NPs fabricated using MF chip have the most uniform morphology, spherical shape, and average diameter of 67 ± 13 nm along with a narrow polydispersity. Conversely, the NP samples prepared via BM method have an irregular and disordered morphology as well as a broad distribution in their particle size (452 ± 300 nm). The in vitro drug release from microfluidically generated CS NPs depicted the controlled release of SK without plateau regime compared to those samples prepared using BM method during 48 h. Also, the drug release kinetic followed Higuchi model which revealed that the Fickian diffusion was the predominant mechanism. Subsequently, in in vivo animal model test, the performance of SK in blood plasma exhibited higher amidolytic activity for SK entrapped in CS NP samples fabricated via MF technique compared to those NPs prepared using BM and also SK alone.