TY - JOUR
T1 - Organosilica colloids as nitric oxide carriers
T2 - Pharmacokinetics and biocompatibility
AU - Chou, Hung Chang
AU - Lo, Chih Hui
AU - Chang, Li Hao
AU - Chiu, Shih Jiuan
AU - Hu, Teh Min
N1 - Funding Information:
The study was supported by the Ministry of Science and Technology , Taiwan (MOST 107–2320-B-010–002 , MOST 108–2320-B-010–037-MY3 , MOST 108–2320-B-010–001 , MOST 108–2320-B-038–044 ) and the Hualien Armed Forces General Hospital ( HAFGH-E-109018 ).
Funding Information:
The study was supported by the Ministry of Science and Technology, Taiwan (MOST 107–2320-B-010–002, MOST 108–2320-B-010–037-MY3, MOST 108–2320-B-010–001, MOST 108–2320-B-038–044), the Hualien Armed Forces General Hospital (HAFGH-E-109018), the Higher Education Sprout Project of the National Yang Ming Chiao Tung University (NYCU) and Ministry of Education (MOE), Taiwan. We acknowledged the support by the Scanning Electron Microscope Facility in NYCU (Department and Institute of Anatomy and Cell Biology) and the Transmission Electron Microscopy Facility in TMU Core Facility Center. The authors would like to thank the Laboratory Animal Center at TMU for technical support in blood chemistry experiments, hematology analysis and animal raising.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Biocompatibility
KW - Colloids
KW - Nanoparticles
KW - Nitric oxide
KW - Organosilica
KW - Pharmacokinetics
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U2 - 10.1016/j.colsurfb.2021.112136
DO - 10.1016/j.colsurfb.2021.112136
M3 - Article
AN - SCOPUS:85116599663
SN - 0927-7765
VL - 208
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
M1 - 112136
ER -