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Synthesis of Pegylated Immunonanoparticles
Oliver, Jean-Christophe,Huertas, Ramon,Lee, Hwa Jeong,Calon, Frederic,Pardridge, William M. 梨花女子大學校 藥學硏究所 2002 藥學硏究論文集 Vol.- No.11
Purpose. This work describes the syrthesis of pesylated immu-nonanoparticies by conjugation of an anti-transferrin receptor mono-clonal antibody (MAb) to maleimide-grafted pegylated nanoparticlesprepared from poly(lactic acid) (PLA) and a hi-functional polyeth-yleneglycol (PEG).Methods. Maleimide-PEG_3500-PLA_4000 and methoxy PEG_2600-PLA_4000 copolymers were synthesized by ring opening polymeriza-tion of L-lactide using stannous octoate as catalyst. Pegylated nano-particles were prepared from these copolymers by a multiple emul-sion/solvent evaporation method and thiolated OX26 MAb wasconjugated through the maleimide function located at the distal endof the PEG spacer. The pegylated immunonanoparticles were char-actenzed by quasi-elastic light scattering, gel permeation chromatog-raphy, turbidimetry assays, and transmission electron microscopy.Results. NMR spectroscopy confirmed the synthesis of both copoly-mers and the preservation of the maleimide function. The pegylatedimmunonanoparticles had an auerage diameter of 121 ± 5 nm andappeared spherical by transmission electron microscopy. The numberof OX26 MAb molecules conjugated per individual pegylated nano-particle was 67 ± 4. The MAb conjugated to the surface of the pe-gylated immunonanoparticle was visualized directly by electron mi-croscopy using a conjugate of 10 nm gold and an anti-mouse immu-noglobulin secondary antibody.Conclusion. Pegylated immunonanopartirles can be synthesized withbifunctional PEG derivatives that bridge the nanoparticle and thetargeting MAb. This novel formulation may enable the targeted de-livery of small molecules, protein drugs, and gene medicines.