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

Author

Listed:
  • Prashant Dogra

    (Houston Methodist Research Institute)

  • Natalie L. Adolphi

    (University of New Mexico)

  • Zhihui Wang

    (Houston Methodist Research Institute
    University of Texas MD Anderson Cancer Center)

  • Yu-Shen Lin

    (University of New Mexico)

  • Kimberly S. Butler

    (University of New Mexico
    University of New Mexico
    Department of Nanobiology)

  • Paul N. Durfee

    (University of New Mexico
    University of New Mexico)

  • Jonas G. Croissant

    (University of New Mexico
    University of New Mexico)

  • Achraf Noureddine

    (University of New Mexico
    University of New Mexico)

  • Eric N. Coker

    (Applied Optical and Plasma Science)

  • Elaine L. Bearer

    (University of New Mexico)

  • Vittorio Cristini

    (Houston Methodist Research Institute
    University of Texas MD Anderson Cancer Center)

  • C. Jeffrey Brinker

    (University of New Mexico
    University of New Mexico
    University of New Mexico
    Self-Assembled Materials Department)

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.

Suggested Citation

  • Prashant Dogra & Natalie L. Adolphi & Zhihui Wang & Yu-Shen Lin & Kimberly S. Butler & Paul N. Durfee & Jonas G. Croissant & Achraf Noureddine & Eric N. Coker & Elaine L. Bearer & Vittorio Cristini & , 2018. "Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06730-z
    DOI: 10.1038/s41467-018-06730-z
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    Cited by:

    1. Thanh Loc Nguyen & Youngjin Choi & Jihye Im & Hyunsu Shin & Ngoc Man Phan & Min Kyung Kim & Seung Woo Choi & Jaeyun Kim, 2022. "Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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