Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 83, Issue 1, Pages 63-75Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2012.09.004
Keywords
Cell uptake; Cisplatin; Intracellular reduction; Polymer-drug conjugates; Prodrug
Categories
Funding
- National Natural Science Foundation of China [21004062, 51103148, 20674084]
- 100 Talents Program of the Chinese Academy of Sciences [KGCX2-YW-802]
- Ministry of Science and Technology of China 973 Project [2009CB930102]
Ask authors/readers for more resources
A polymeric cisplatin(IV) prodrug in the form of cross-linked micelles (M(Pt(IV)) was prepared by first constructing MPEG-b-PCL-b-PLL micelles and then attaching a cisplatin(IV) complex with two axial succinic moieties to the lysine residues of the carrier polymer in aqueous medium. The micelles obtained were characterized by TEM, DLS, and zeta potential measurement. Their in vitro release experiments were carried out at pH 7.4 and 5.0 or in the presence of 5 mM sodium ascorbate (NaAsc). Results showed that the micelles were sensitive to both acidic hydrolysis and mild reducing agents; in the presence of 5 mM NaAsc, cisplatin(II) was directly released and the released cisplatin(II) could chelate with nucleobases; the micelles displayed comparable cytotoxicities to cisplatin; and the micelles were much more efficiently internalized by the cells than cisplatin(II) and cisplatin(IV) counterparts. Moreover, in vivo study showed accumulation of more Pt species in the tumor site and lower systematic toxicity compared to free cisplatin(II) and cisplatin(IV). This polymeric prodrug of cisplatin is expected to be used more for future study and applications. (c) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available