Complement activation by model drug carriers for intravenous application: determination by two-dimensional electrophoresis

Citation
M. Luck et al., Complement activation by model drug carriers for intravenous application: determination by two-dimensional electrophoresis, BIOMATERIAL, 20(21), 1999, pp. 2063-2068
Citations number
35
Categorie Soggetti
Multidisciplinary
Journal title
BIOMATERIALS
ISSN journal
01429612 → ACNP
Volume
20
Issue
21
Year of publication
1999
Pages
2063 - 2068
Database
ISI
SICI code
0142-9612(199911)20:21<2063:CABMDC>2.0.ZU;2-Y
Abstract
The interactions of intravenously injected drug carriers with blood protein s are considered as an important factor for the fate of the particles after their administration. Protein adsorption on latex particles applied as mod el for intravenous drug carriers was analysed using two-dimensional electro phoresis (2-DE). The particles were incubated in citrated plasma, serum and heat-inactivated serum, respectively. Incubation in the various media resu lted in clear differences in the protein adsorption patterns. Two character istic protein spots were determined to be enriched on the 2-DE gels only af ter incubation of the particles in serum. Employing N-terminal microsequenc ing these protein spots were identified to be fragments of the complement p rotein C3. Enrichment of these particular spots was most likely a result of complement activation by the particles. Mechanism of C3 binding to the par ticle surface and subsequent inactivation by cleavage are discussed in orde r to explain the results. It could be demonstrated that 2-DE analysis provi des the possibility to distinguish between adsorption and covalent attachme nt of C3 to particulate surfaces. The findings indicate that complement act ivation was caused by covalent binding of the C3 component C3b to the parti cles' surface. The influence of the incubation medium on the in vitro prote in adsorption of particulate drug carriers has to be considered when a corr elation between the protein adsorption pattern and the in vivo behaviour of the particles is approached. (C) 1999 Elsevier Science Ltd. All rights res erved.