TY - JOUR
T1 - Fast processes of nanoparticle blood clearance
T2 - Comprehensive study
AU - Zelepukin, Ivan V.
AU - Yaremenko, Alexey V.
AU - Yuryev, Mikhail V.
AU - Mirkasymov, Aziz B.
AU - Sokolov, Ilya L.
AU - Deyev, Sergey M.
AU - Nikitin, Petr I.
AU - Nikitin, Maxim P.
PY - 2020/10/10
Y1 - 2020/10/10
N2 - Blood circulation is the key parameter that determines the in vivo efficiency of nanoagents. Despite clinical success of the stealth liposomal agents with their inert and shielded surfaces, a great number of non-stealth nanomaterials is being developed due to their potential of enhanced functionality. By harnessing surface phenomena, such agents can offer advanced control over drug release through intricately designed nanopores, catalysis-propelled motion, computer-like analysis of several disease markers for precise target identification, etc. However, investigation of pharmacokinetic behavior of these agents becomes a great challenge due to ultra-short circulation (usually around several minutes) and impossibility to use the invasive blood-sampling techniques. Accordingly, the data on circulation of such agents has been scarce and irregular. Here, we demonstrate high-throughput capabilities of the developed magnetic particle quantification technique for nanoparticle circulation measurements and present a comprehensive investigation of factors that affect blood circulation of the non-stealth nanoparticles. Namely, we studied the following 9 factors: particle size, zeta-potential, coating, injection dose, repetitive administration, induction of anesthesia, mice strain, absence/presence of tumors, tumor size. Our fundamental findings demonstrate potential ways to extend the half-life of the agents in blood thereby giving them a better chance of achieving their goal in the organism. The study will be valuable for design of the next generation nanomaterials with advanced biomedical functionality.
AB - Blood circulation is the key parameter that determines the in vivo efficiency of nanoagents. Despite clinical success of the stealth liposomal agents with their inert and shielded surfaces, a great number of non-stealth nanomaterials is being developed due to their potential of enhanced functionality. By harnessing surface phenomena, such agents can offer advanced control over drug release through intricately designed nanopores, catalysis-propelled motion, computer-like analysis of several disease markers for precise target identification, etc. However, investigation of pharmacokinetic behavior of these agents becomes a great challenge due to ultra-short circulation (usually around several minutes) and impossibility to use the invasive blood-sampling techniques. Accordingly, the data on circulation of such agents has been scarce and irregular. Here, we demonstrate high-throughput capabilities of the developed magnetic particle quantification technique for nanoparticle circulation measurements and present a comprehensive investigation of factors that affect blood circulation of the non-stealth nanoparticles. Namely, we studied the following 9 factors: particle size, zeta-potential, coating, injection dose, repetitive administration, induction of anesthesia, mice strain, absence/presence of tumors, tumor size. Our fundamental findings demonstrate potential ways to extend the half-life of the agents in blood thereby giving them a better chance of achieving their goal in the organism. The study will be valuable for design of the next generation nanomaterials with advanced biomedical functionality.
KW - Blood circulation time
KW - Macrophages
KW - Magnetic detection
KW - Nanoparticles
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85088240879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088240879&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.07.014
DO - 10.1016/j.jconrel.2020.07.014
M3 - Article
C2 - 32681949
AN - SCOPUS:85088240879
VL - 326
SP - 181
EP - 191
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -