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Cholesterol Modification of an Anticancer Drug for Efficient Incorporation into a Supramolecular Hydrogel System
Author(s) -
Bakker Maarten H.,
Grillaud Maxime,
Wu Dan Jing,
Fransen PeterPaul K. H.,
de Hingh Ignace H.,
Dankers Patricia Y. W.
Publication year - 2018
Publication title -
macromolecular rapid communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 154
eISSN - 1521-3927
pISSN - 1022-1336
DOI - 10.1002/marc.201800007
Subject(s) - lipophilicity , mitomycin c , drug delivery , supramolecular chemistry , combinatorial chemistry , drug , chemistry , cholesterol , drug carrier , pharmacology , stereochemistry , organic chemistry , biochemistry , molecule , medicine , surgery
Treatment of cancer in the peritoneal cavity may be improved with macroscale drug delivery systems that offer control over intraperitoneal concentration of chemotherapeutic agents. Currently, suitable drug carriers to facilitate a sustained release of small hydrophilic drugs such as mitomycin C are lacking. For this purpose, a pH‐responsive supramolecular hydrogel based on ureido‐pyrimidinone (UPy) chemistry is utilized here. In order to provide a sustained release profile, a lipophilicity‐increasing cholesterol conjugation strategy is proposed that enhances affinity between the modified drug (mitomycin‐PEG 24 ‐cholesterol, MPC) and the hydrophobic compartments in the UPy gel. Additional advantages of cholesterol conjugation include improved chemical stability and potency of mitomycin C. In vitro the tunability of the system to obtain optimal effective concentrations over time is demonstrated with a combinatorial treatment of mitomycin C and MPC in one UPy hydrogel delivery system.