Targeting efficiency of PEG-immunoliposome-conjugated antibodies at PEG terminals

doi:10.1016/S0169-409X(96)00463-2

Advanced Drug Delivery Reviews

Volume 24, Issues 2–3, 17 March 1997, Pages 235-242

https://doi.org/10.1016/S0169-409X(96)00463-2 Get rights and content

Abstract

We have developed a new type of PEG-immunoliposome carrying monoclonal antibodies or their fragments (F(ab′)2, Fab′) at the distal ends of the PEG chains (Type C). Distearoylphosphatidylethanolamine derivatives of PEG with car☐yl group (DSPE-PEG-COOH) or dipalmitoyl phosphatidylethanolamine derivatives of PEG with maleimidyl group (DPPE-PEG-Mal) at the PEG terminal were newly synthesized. Small unilamellar liposomes (90–130 nm in diameter) were prepared from distearoyl phosphatidylcholine and cholesterol (2:1, m/m) containing 6 mol% of DSPE-PEG-COOH or DPPE-PEG-Mal. To target to the vascular endothelial lung surface as a model accessible site, 34A antibody, which is highly specific to mouse pulmonary endothelial cells, was conjugated to PEG-liposome (34A-Type C). The degree of lung binding of 34A-Type C in BALB/c mice was significantly higher than that of the 34A-Type A which is an ordinary type immunoliposome (without PEG derivatives). To target to the solid tumor tissue as a model of the less accessible site, 21B2 antibody which is anti-human CEA and its Fab′ fragment were used. The targeting ability of Fab′-Type C was examined by using CEA-positive human gastric cancer strain MKN-45 cells inoculated into BALB/c nu/nu mice. Fab′-Type C showed the low RES uptake and the long circulation time, and resulted in enhanced accumulation of the liposomes in the solid tumor. The small Fab′-Type C could predominantly pass through the leaky tumor endothelium by passive convective transport.

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Targeting efficiency of PEG-immunoliposome-conjugated antibodies at PEG terminals

Abstract

Biochim. Biophys. Acta

J. Pharm. Sci.

FEBS Lett.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

FEBS Lett

Biochim. Biophys. Acta

Crit. Rev. Oncol. Hematol.

Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo