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Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab’ fragments

Paper ID Volume ID Publish Year Pages File Format Full-Text
10568 691 2007 13 PDF Available
Title
Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab’ fragments
Abstract

Immunonanocapsules were synthesized by conjugation to lipid nanocapsules (LNC) of whole OX26 monoclonal antibodies (OX26 MAb) directed against the transferrin receptor (TfR). The TfR is overexpressed on the cerebral endothelium and mediates the transcytosis mechanism. Fab’ fragments, known for their reduced interaction with the reticuloendothelial system, were also conjugated to LNC. This coupling was facilitated by the incorporation of lipid PEG2000 functionalized with reactive-sulfhydryl maleimide groups (DSPE–PEG2000–maleimide) into LNC shells by a post-insertion procedure, developed initially for liposome pegylation. An interfacial model using the dynamic rising drop technique helped determine the parameters influencing the DSPE–PEG2000–maleimide insertion and the quality of the anchorage. Heat was essential to promote both an important and stable adsorption of DSPE–PEG2000–maleimide onto LNC. OX26 MAb were thiolated to react with maleimide functions whereas thiol residues on Fab’ fragments were used directly. The number of ligands per nanocapsule was adjusted according to their initial quantity in the coupling reaction mixture, with densities from 16 to183 whole antibodies and between 42 and 173 Fab’ fragments per LNC. The specific association of immunonanocapsules to cells overexpressing TfR was thus demonstrated, suggesting their ability to deliver drugs to the brain.

Keywords
Immunonanocapsules; Ox26 monoclonal antibody; Fab’ fragment; Transferrin receptor; Brain targeting; Interfacial rheology
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Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab’ fragments
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 33, November 2007, Pages 4978–4990
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
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Full-text PDF Download
Online Support
Any Questions? feel free to contact us