Colloidal carriers for intravenous drug targeting: plasma protein adsorption patterns on surface-modified latex particles evaluated by two-dimensional polyacrylamide gel electrophoresis.
Targeting to specific sites of the body via colloidal carriers is sought in order to reduce drug side effects. The adsorption of plasma proteins on intravenously injected particles is regarded as the key factor in explaining their organ distribution: total bound protein, or, more likely, the presence of specific proteins and their conformation, are expected to influence macrophage uptake. Polystyrene beads, 60 nm in diameter, were used as model carriers; their surface was differentially modified by adsorption of increasingly hydrophilic block copolymers, poloxamers 184, 188 and 407. After incubation in plasma, the patterns of protein adsorption onto coated beads were analyzed by high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The behavior of some representative proteins was monitored, including albumin, fibrinogen, IgG, factor B and the apolipoproteins, A-I, A-IV, C-III, E and J. The more hydrophobic the particles, the larger the total amount of bound protein. However, this correlation was not valid for all of the analyzed protein species, which proves that it is insufficient to look only at physicochemical data to predict organ distribution. On the contrary, it is essential to use 2-D PAGE to establish the correlation between adsorbed proteins and carrier behavior in vivo.
Blunk
T
T
Department of Pharmaceutics and Biopharmaceutics, University of Kiel, Germany.
Hochstrasser
D F
DF
Sanchez
J C
JC
Müller
B W
BW
Müller
R H
RH
D000327:Adsorption; D001053:Apolipoproteins / Q000032:analysis; D001798:Blood Proteins / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003102:Colloids; D011415:Complement Factor B / Q000032:analysis; D004337:Drug Carriers; D015180:Electrophoresis, Gel, Two-Dimensional; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D008863:Microspheres; D011137:Polystyrenes / Q000737:chemistry; D014168:Transferrin / Q000032:analysis
D001053:Apolipoproteins; D001798:Blood Proteins; D003102:Colloids; D004337:Drug Carriers; D011137:Polystyrenes; D014168:Transferrin; D005340:Fibrinogen; D011415:Complement Factor B