Development, Evaluation, and Characterization of Aprotinin Loaded Mesoporous Silica Nanoparticles to Impede Uncontrolled Bleeding
摘要
The availability of many hemostatic agents is associated with various adverse effects that make them unsuitable for use. The current work was designed to overcome these challenges by incorporating aprotinin (AP) into mesoporous silica (MS) nanoparticles. The Stober method was implied to prepare AP-loaded mesoporous silica (AP-MS) nanoparticles. Design Expert® version 12 was applied for optimization by analyzing the effect of independent variables, i.e., ethanol, ammonia, and tetra ethyle orthosilicate (TEOS) on particle size, and entrapment efficiency. The optimized AP-MS nanoparticles had an average particle size of 203 ± 5.94 nm and entrapment efficiency of 87 ± 1.53%. The Fourier transform infrared spectroscopy analysis confirmed the presence of all significant peaks of AP in AP-MS nanoparticles. In X-ray diffraction, the characteristic peaks of AP were absent in AP-MS nanoparticles, confirming their amorphous nature. AP-MS nanoparticles released 99% AP in 12 h compared to AP-Solution in 2 h. Ex vivo blood coagulation clotting time was 3.2 ± 4.35 s, which was much less when compared to all other groups. Hemt was significantly short as 94 ± 6.78 s followed by a low quantity of blood loss of 0.33 ± 0.03 mg compared to all other groups in the rat tail vein model. The histopathological study confirmed the non-toxic effect of AP-MS nanoparticles on major organs like the heart, kidney, and liver compared to all other groups. These findings highlight the promising potential of AP-MS nanoparticles as a safe and efficient delivery system for controlling uncontrolled bleeding, offering significant improvements over traditional hemostatic agents.
Graphical Abstract