CDDP supramolecular micelles fabricated from adamantine terminated mPEG and β-cyclodextrin based seven-armed poly (L-glutamic acid)/CDDP complexes.
This research is aimed to develop a nano-sized supramolecular micelle delivery system of cis-dichlorodiammine platinum (II) (CDDP) in order to achieve the passive tumor targeting. Firstly, star-shaped poly (γ-benzyl-L-glutamate) was synthesized by the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride initiated with per-6-amino-β-cyclodextrin. After removal of benzyl groups, β-cyclodextrin based seven-armed poly (L-glutamic acid) (β-CD-7PLGA) was obtained. β-CD-7PLGA/CDDP complexes were prepared by the complex reaction between the carboxylic groups of β-CD-7PLGA and CDDP. Further inclusion of β-CD-7PLGA/CDDP complexes with adamantine terminated mPEG (mPEG-Ad) gave CDDP supramolecular micelles (mPEG-Ad@β-CD-7PLGA/CDDP). The formation of mPEG-Ad@β-CD-7PLGA/CDDP supramolecular micelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. All the micelles showed spherical shape, and their sizes increased from 100 to 135 nm with the increase of PLGA arm molecular weight. mPEG-Ad@CD-7PLGA/CDDP micelles showed sustained drug release profiles over 50h in PBS. Compared with CDDP, mPEG-Ad@β-CD-7PLGA/CDDP supramolecular micelles showed essential decreased cytotoxicity to KB cells, suggesting their great potential as the delivery carriers of CDDP.
Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China.
Dawei
D
Yong
Yu
Y
Luo
Fang
F
Du
Jin
J
Huang
Wei
W
Lu
Zhaoyun
Z
Dai
Jiahui
J
Yu
Shiyuan
S
Liu
D000547:Amantadine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D007624:KB Cells / Q000187:drug effects* / Q000473:pathology; D008823:Micelles; D008970:Molecular Weight; D053758:Nanoparticles / Q000008:administration & dosage; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011099:Polyglutamic Acid / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D015259:Dopamine Agents; D008823:Micelles; D047392:beta-Cyclodextrins; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D000547:Amantadine; C031215:betadex; D002945:Cisplatin