Constructing a Biomaterial to Simulate Extracellular Drug Transport in Solid Tumors.
Designing an in vitro model of the tumor extracellular microenvironment to screen intratumoral drugs is an active challenge. As recent clinical successes of human intratumoral therapies stimulate research on intratumoral delivery, a need for a 3D tumor model to screen intratumoral therapies arises. When injecting the drug formulation directly into the tumor, the biophysics affecting intratumoral retention must be considered; especially for biologic therapies, which may be dominated by extracellular transport mechanisms. Fibrotic regions in solid tumors are typically rich in collagen I fibers. Using shear rheology, head and neck tumors with higher collagen density show a higher stiffness. Similarly, the stiffness of the hyaluronic acid (HA) hydrogel models is increased by adding collagen fibers to model the bulk biomechanical properties of solid tumors. HA hydrogels are then used as intratumoral injection site simulators to model in vitro the retention of glatiramer acetate (GA) and polyethylene glycol (PEG) administered intratumorally. Both compounds are also injected in murine tumors and retention is studied ex vivo for comparison. Retention of GA in the hydrogels is significantly longer than PEG, analogous to the solid tumors, suggesting the utility of HA hydrogels with collagen I fibers for screening extracellular drug transport after intratumoral administration.
['Huayamares|Sebastian G|SG|0000-0003-2859-3074', 'Song|Jimmy Y|JY|', 'Huang|Aric|A|', 'Crowl|Samuel R|SR|', 'Groer|Chad E|CE|0000-0002-8589-9304', 'Forrest|M Laird|ML|', 'Berkland|Cory J|CJ|0000-0002-7164-7886']
D000818:Animals D001672:Biocompatible Materials D045744:Cell Line, Tumor D004337:Drug Carriers D004339:Drug Compounding D016503:Drug Delivery Systems D000068717:Glatiramer Acetate D006258:Head and Neck Neoplasms D006801:Humans D006820:Hyaluronic Acid D020100:Hydrogels D051379:Mice D011092:Polyethylene Glycols D023041:Xenograft Model Antitumor Assays
intratumoral therapy hydrogels injection site simulator drug delivery intratumoral drug transport