Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

Dogra, Prashant; Adolphi, Natalie L.; Wang, Zhihui; Lin, Yu-Shen; Butler, Kimberly S.; Durfee, Paul N.; Croissant, Jonas G.; Noureddine, Achraf; Coker, Eric N.; Bearer, Elaine L.; Cristini, Vittorio; Brinker, C. Jeffrey

doi:10.1038/s41467-018-06730-z

Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

Journal Article · Wed Oct 31 00:00:00 EDT 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-06730-z· OSTI ID:1619781

Dogra, Prashant; Adolphi, Natalie L.; ; Lin, Yu-Shen; Butler, Kimberly S.; ; ; ; ; Bearer, Elaine L.; Cristini, Vittorio; Brinker, C. Jeffrey

Abstract

The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: NA0003525

OSTI ID:: 1619781

Alternate ID(s):: OSTI ID: 1492391

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 9; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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