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Synthesis of pegylated immunonanoparticles
- Synthesis of pegylated immunonanoparticles
- Olivier, JC; Huertas, R; Lee, HJ; Calon, F; Pardridge, WM
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- PHARMACEUTICAL RESEARCH
- vol. 19, no. 8, pp. 1137 - 1143
- polyethylene glycol; maleimide; immunonanoparticle; monoclonal antibody; brain drug targeting
- KLUWER ACADEMIC/PLENUM PUBL
- SCI; SCIE; SCOPUS
- 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.
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