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Synthesis of pegylated immunonanoparticles

Title
Synthesis of pegylated immunonanoparticles
Authors
Olivier, JCHuertas, RLee, HJCalon, FPardridge, WM
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2002
Journal Title
PHARMACEUTICAL RESEARCH
ISSN
0724-8741JCR Link
Citation
vol. 19, no. 8, pp. 1137 - 1143
Keywords
polyethylene glycolmaleimideimmunonanoparticlemonoclonal antibodybrain drug targeting
Publisher
KLUWER ACADEMIC/PLENUM PUBL
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Purpose. This work describes the synthesis of pegylated immunonanoparticles by conjugation of an anti-transferrin receptor monoclonal antibody (MAb) to maleimide-grafted pegylated nanoparticles prepared from poly(lactic acid) (PLA) and a bi-functional polyethyleneglycol (PEG). Methods. Maleimide-PEG(3500)-PLA(40000) and methoxyPEG(2)600-PLA(4)0000 copolymers were synthesized by ring opening polymerization of L-lactide using stannous octoate as catalyst. Pegylated nanoparticles were prepared from these copolymers by a multiple emulsion/solvent evaporation method and thiolated OX26 MAb was conjugated through the maleimide function located at the distal end of the PEG spacer. The pegylated immunonanoparticles were characterized by quasi-elastic light scattering, gel permeation chromatography, turbidimetry assays, and transmission electron microscopy. Results. NMR spectroscopy confirmed the synthesis of both copolymers and the preservation of the maleimide function. The pegylated immunonanoparticles had an average diameter of 121 +/- 5 nm and appeared spherical by transmission electron microscopy. The number of OX26 MAb molecules conjugated per individual pegylated nanoparticle was 67 +/- 4. The MAb conjugated to the surface of the pegylated immunonanoparticle was visualized directly by electron microscopy using a conjugate of 10 nm gold and an anti-mouse immunoglobulin secondary antibody. Conclusion. Pegylated immunonanoparticles can be synthesized with bifunctional PEG derivatives that bridge the nanoparticle and the targeting MAb. This novel formulation may enable the targeted delivery of small molecules, protein drugs, and gene medicines.
DOI
10.1023/A:1019842024814
Appears in Collections:
약학대학 > 약학과 > Journal papers
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