Cholesterol modification of an anticancer drug for efficient incorporation into a supramolecular hydrogel system

Maarten H. Bakker, Maxime Grillaud, Dan Jing Wu, Peter Paul K.H. Fransen, Ignace H. de Hingh, Patricia Y.W. Dankers

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
50 Downloads (Pure)

Abstract

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-PEG24-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.

Original languageEnglish
Article number1800007
Number of pages6
JournalMacromolecular Rapid Communications
Volume39
Issue number17
DOIs
Publication statusPublished - Sep 2018

Keywords

  • Cholesterol
  • Controlled release
  • Drug delivery
  • Intraperitoneal chemotherapy
  • Mitomycin C
  • Supramolecular hydrogel
  • Mitomycin/chemistry
  • Cholesterol/chemistry
  • Humans
  • Structure-Activity Relationship
  • Cell Survival/drug effects
  • Dose-Response Relationship, Drug
  • Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry
  • Cell Death/drug effects
  • Molecular Structure
  • Cell Proliferation/drug effects
  • Urea/analogs & derivatives
  • Antibiotics, Antineoplastic/chemistry
  • Polyethylene Glycols/chemistry
  • Cell Line, Tumor
  • Hydrophobic and Hydrophilic Interactions
  • Pyrimidinones/chemistry
  • Macromolecular Substances/chemistry
  • Drug Screening Assays, Antitumor
  • Hydrogen-Ion Concentration
  • mitomycin C
  • drug delivery
  • intraperitoneal chemotherapy
  • cholesterol
  • controlled release
  • supramolecular hydrogel

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