Organosilica colloids as nitric oxide carriers: Pharmacokinetics and biocompatibility

Nitric oxide (NO) is a potential therapeutic agent for various diseases. However, it is challenging to deliver this unstable, free-radical gaseous molecule in the body. Various nanoparticle-based drug delivery systems have been investigated as promising NO carriers without detailed characterization of their biological fate. The purpose of this study is to investigate the pharmacokinetics and biocompatibility of organosilica-based NO-delivering nanocarriers. Two distinct NO nanoformulations, namely NO-SiNP-1 and NO-SiNP-2, were prepared from a thiol-functionalized organosilane using nanoprecipitation and direct aqueous synthesis, respectively. During the preparation, the thiol group was converted to S-nitrosothiol (SNO) under a nitrosation condition. The final products contain SNO-loaded organosilica particles of similar sizes (~130 nm), but of different morphologies and surface charges (between the two formulations). In the in vitro release kinetics study, NO-SiNP-1 exhibited a much slower NO release rate than NO-SiNP-2 (by 5-fold); therefore, the former is considered as a slow NO releaser, and the latter a fast NO releaser. However, in the rat pharmacokinetic study (IV bolus of 50 μmol/kg), NO-SiNP-1 was rapidly eliminated from the blood (within 20 min); in contrast, NO-SiNP-2 was slowly eliminated with an extended circulation time of 12 h for plasma SNO, along with markedly higher plasma levels of nitrite and nitrate. The two formulations are generally biocompatible. In conclusion, the paper presents contrast biological fates of two organosilica colloidal formulations for nitric oxide delivery.