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Abstract Drug delivery systems have renewed attention in recent years to achieve targeted delivery while decreasing toxic side effects. However, there are many factors that prevent optimal administration of drug delivery particles. For instance, protein corona formation and aggregation both decrease the circulation half‐life of drug delivery particles, leading to sequestration to the liver and spleen. Therefore, optimal surface modifications are needed to decrease protein corona formation and avoid aggregation. In this work, polystyrene particles were modified with multi‐arm and linear polyethylene glycol (PEG) to determine their aggregation profiles and protein corona formation. Multi‐arm PEGs were found to aggregate more than linear PEGs, due to the change in zeta potential from unreacted end groups, which may lead to shorter circulation half‐lives. Furthermore, the protein corona formation and composition were studied after different washing procedures, highlighting the importance of studying protein corona formation with undiluted blood plasma.
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Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics
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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- Award ID(s):
- 1716737
- PAR ID:
- 10154295
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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