Preparation and in vitro targeting of sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody / 药学学报
Acta Pharmaceutica Sinica
;
(12): 506-512, 2006.
Article
in English
| WPRIM
| ID: wpr-271417
ABSTRACT
<p><b>AIM</b>To prepare sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody (chTNT-3) and investigate their immunoreactivity and in vitro targeting.</p><p><b>METHODS</b>An end-group functionalized polyethylene glycol-lipid derivative (pyridylthiopropionoylamino-polyethylene glycol-hydrogenated soy phosphatidylethanolamine, PDP-PEG-HSPE) was synthesized and incorporated to sterically stabilized liposomes. After mild thiolysis of the PDP groups by dithiothreitol, liposomes were covalently linked with maleimide-derivatized chTNT-3 and formed sterically stabilized immunoliposomes. Coupling efficiency, antibody density, size distribution, immunoreactivity of chTNT-3-modified sterically stabilized liposomes (chTNT-3-SLs) and specific binding properties of the chTNT-3-SLs to fixed Raji cells were determined, separately.</p><p><b>RESULTS</b>Higher initial Ab/PDP-PEG-HSPE molar ratios resulted in higher antibody density on the surface of liposomes but lower coupling efficiency. The optimal coupling efficiency of 71% was obtained while antibody density in liposome was 106 microg antibody/micromol phospholipids (as initial antibody/PDP-PEG-HSPE = 1 10). The chTNT-3-SLs had a narrow size distribution after extrusion and the mean size of this immunoliposomes was (115 +/- 33) nm. The immunoreactivity of chTNT-3 can be preserved after efficient attachment of maleimide-derivatized chTNT-3 to the surface of liposomes. But calculated per antibody concentration, the immunoreactivity of chTNT-3-SLs would obviously decrease compared to that of chTNT-3 or chTNT-3 derivatives. Significantly higher binding of chTNT-3-SLs to fixed Raji cells directed by chTNT-3 was obtained compared to other preparations in serial dilutions (P < 0.01).</p><p><b>CONCLUSION</b>chTNT-3-SLs prepared by PDP-PEG-HSPE method remained most immunoreactivity of chTNT-3 and was able to bind nuclear antigens in vitro.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Phosphatidylethanolamines
/
Polyethylene Glycols
/
Binding Sites
/
Drug Carriers
/
Lymphoma, B-Cell
/
Drug Delivery Systems
/
Cell Line, Tumor
/
Allergy and Immunology
/
Liposomes
Limits:
Humans
Language:
English
Journal:
Acta Pharmaceutica Sinica
Year:
2006
Type:
Article
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