Development of a novel method for albumin-based nanoparticle preparation using sulfosalicylic acid for the treatment of sepsis

<p>【Purpose】Human serum albumin (HSA) with long blood retention is ideal material to fabricate nanoparticles for drug delivery. However, we revealed that desolvation method which is one of HSA-nanoparticule method is caused to decrease the blood half-life of HSA via conformational change of HSA by disulfide reduction. To develop the method for HSA-nanoparticle with long blood retention, we developed the sulfosalicylic acid-HSA nanoparticle (SSA-HSAnp) method and investigated the kinetic and biological properties.</p><p>【Method】SSA-HSAnp was prepared by mixing SSA and HSA. The blood retention evaluation of SSA-HSAnp and its protective effect on LPS-induced sepsis were investigated in vivo.</p><p>【Results and Discussion】The concentration of SSA was finely tuned to produce particles without precipitate, and SSA-HSAnp was successfully prepared with a size-adjustable particle between 30-100 nm. The kinetics result showed that SSA-HSAnp possesses the blood retention similar to HSA. Therefore, we have successfully produced HSAnp that possesses the blood retention of original HSA. Interestingly, SSA-HSAnp suppressed LPS-induced NO production more powerful than original HSA both in vitro and in vivo experiments. We are going to analyze the inhibited mechanism of NO production by SSA-HSAnp. These results indicate that SSA-HSAnp can be a useful drug carrier that possesses not only blood retention properties of original HSA but superior anti-oxidative activity.</p>