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Effect of PEO surface density on long-circulating PLA-PEO nanoparticles which are very low complement activators
The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MRS) is a major obstacle when a long blood circulation time is needed. Whereas nanoparticles made from PLA and stabilized by surfactants (PLA-F68) are rapidly phagocytized, the rate of phagocytosis is strongly...
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Published in: | Biomaterials 1996, Vol.17 (16), p.1575-1581 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MRS) is a major obstacle when a long blood circulation time is needed. Whereas nanoparticles made from PLA and stabilized by surfactants (PLA-F68) are rapidly phagocytized, the rate of phagocytosis is strongly reduced in case of nanoparticles made from a diblock copolymer (PLA-PEO). Because of the role of the complement system in opsonization, this difference of phagocytosis was hypothesized to be related to this system. An important complement consumption was obtained in 5 min in the presence of PLA-F68 particles. In the presence of a higher surface area of PLA-PEO particles possessing a high PEO surface density, the consumption remained very low. When the average PEO surface density was decreased on such particles below a given threshold, a fast and strong complement consumption occurred again. These experimental data support the concept of steric repulsion towards proteins, by surfaces covered with terminally attached PEO chains and emphasize the prime importance of PEO surface density in such an effect. The major, but probably not exclusive, role of complement as an opsonin capable of inducing a fast phagocytosis by MPS should be taken into account concerning the
in vitro evaluation of nanoparticles as candidates for a long blood circulation. |
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ISSN: | 0142-9612 1878-5905 |
DOI: | 10.1016/0142-9612(95)00322-3 |