title: A stimuli-responsive hydrogel for doxorubicin delivery.
abstract: The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion-exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.
authors.affiliation: Departments of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.forename: Zen
authors.initials: Z
authors.lastname: Liu
authors.forename: Matthias
authors.initials: M
authors.lastname: Pumberger
authors.forename: Catalina Vallejo
authors.initials: CV
authors.lastname: Giraldo
authors.forename: Terry
authors.initials: T
authors.lastname: Ruesink
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019245:Compressive Strength / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005612:Freeze Drying; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008689:Methacrylates / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D003432:Cross-Linking Reagents; D008689:Methacrylates; C008384:methacrylic acid; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004317:Doxorubicin