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In vitro evaluation of nanoparticles spleen capture
M Demoy1, J P Andreux, C Weingarten
1Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, URA CNRS 1218, Faculté de Pharmacie, Université Paris XI, Châtenay-Malabry, France.
Life Sciences
|May 5, 1999
Summary
This study introduces an in vitro spleen slice model to investigate nanoparticle uptake by marginal zone macrophages. Results show scavenger receptors and albumin are key in nanoparticle capture, offering a new assay for drug carriers.
Area of Science:
- Nanomedicine
- Immunology
- Cell Biology
Background:
- Spleen macrophages capture intravenously injected nanoparticles, primarily in the marginal zone.
- Traditional cell preparation methods damage these macrophages, hindering in vitro study.
- A novel tissue slice incubation method is needed to study nanoparticle-macrophage interactions in vivo-like conditions.
Purpose of the Study:
- To develop and validate an in vitro spleen slice model for studying nanoparticle-macrophage interactions.
- To elucidate the mechanisms underlying nanoparticle capture by splenic marginal zone macrophages.
- To establish a reliable assay for evaluating nanoparticulate drug carrier interactions with the spleen.
Main Methods:
- Development of an in vitro spleen tissue slice incubation method.
- Incubation of spleen slices with nanoparticles in serum-supplemented and depleted media.
- Assessment of nanoparticle uptake using various blocking agents and competitive ligands.
Main Results:
- The in vitro model accurately reflects in vivo nanoparticle uptake profiles.
- Complement, immunoglobulins, and heparin-binding proteins did not significantly affect nanoparticle capture.
- Albumin substitution in serum allowed near-optimal uptake, and scavenger receptor blockers strongly reduced spleen capture.
Conclusions:
- The developed in vitro spleen slice assay is a valid method for studying nanoparticle-spleen interactions.
- Nanoparticle capture by the spleen is a complex, multifactorial process.
- Albumin and scavenger receptors play a significant role in the spleen's capture of nanoparticles.