Silk-Elastinlike Protein Polymer Liquid Chemoembolic for Localized Release of Doxorubicin and Sorafenib.
Locoregional therapies for cancer are minimally invasive procedures in which the treatment is administered directly into cancerous tissue. Transarterial chemoembolization (TACE) is used to treat intermediate stage hepatocellular carcinoma (HCC). TACE uses an embolic material to block blood flow while coadministering a chemotherapeutic to the neoplastic tissue. Liquid embolics capable of drug loading are at the forefront of development as they allow for deeper permeation of tumor vasculature, increase neoplasm exposure to therapeutics, and resist revascularization by occupying both large and small diameter vessels. In this work, two chemotherapeutics used in the treatment of HCC, doxorubicin and sorafenib, were incorporated into the in situ gelling liquid embolic composed of a silk-elastinlike protein polymer (SELP-815 K). The base forms of the drugs had no significant effect on the viscosity, the gelation kinetics, and the gel stiffness of the SELP: all properties essential for the successful performance of an injectable liquid embolic. In vitro release studies indicated that the SELP liquid embolic delivered doxorubicin and sorafenib, either alone or in combination, at therapeutically relevant concentrations for a minimum of 14 and 30 days, respectively.
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.|Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States.
Azadeh
A
Poursaid
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.|Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States.
Mark Martin
MM
Jensen
Department of Biology, University of Utah , Salt Lake City, Utah 84112, United States.
Ida
I
Nourbakhsh
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.
Mitchell
M
Weisenberger
Merit Medical Systems, Inc. , South Jordan, Utah 84095, United States.
John W
JW
Hellgeth
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.|Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States.
Sujatha
S
Sampath
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
Joseph
J
Cappello
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.|Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
Hamidreza
H
Ghandehari
D004317:Doxorubicin / Q000737:chemistry*; D065546:Drug Liberation; D008855:Microscopy, Electron, Scanning; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry; D010671:Phenylurea Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012212:Rheology; D047011:Silk / Q000737:chemistry*; D000077157:Sorafenib; D017550:Spectroscopy, Fourier Transform Infrared
D010671:Phenylurea Compounds; D011108:Polymers; D047011:Silk; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib
embolization; hepatocellular carcinoma; silk-elastinlike protein polymer (SELP); transarterial chemoembolization (TACE)