Controlled release of sunitinib in targeted cancer therapy: smart magnetically responsive hydrogels as restricted access materials

Abstract

The aim of the present work was the preparation of a magnetic hydrogel for guided release of sunitinib malate (SUM), an anticancer drug. Precipitation polymerization method has been employed in order to synthesize the hydrogel, using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), glycidyl methacrylate (GMA) and 2,2 0 -azobisisobutyronitrile (AIBN) as monomer, cross-linker, pro-hydrophilic monomer and initiator, respectively. To confer magnetic responsiveness, particles of magnetite have been encapsulated during the polymerization process, followed by epoxide ring opening on the nanospheres' surface, in order to obtain a restricted access material (RAM) with low protein adsorption ability and improved biocompatibility. The successful introduction of magnetite has been confirmed through FT-IR and TG analyses, while protein adsorbing tests have been conducted to verify the RAM features. Furthermore, swelling properties have been evaluated before and after epoxide ring opening. Finally, in vitro tests have been performed to evaluate the release profile and cytotoxic effect on ARO, WRO, HeLa and MCF-7 cell lines.

Molecularly Imprinted Polymers (MIPs) as Theranostic Systems for Sunitinib Controlled Release and Self-Monitoring in Cancer Therapy

“…log(Q e − Q t ) = log(Q e ) − K 1 2.303 t (10) in which Q e is the amount of adsorbed SUT at the equilibrium time, K 1 represents the first-order adsorption rate constant, and t is the adsorption time. This model is based on the assumption that one molecule adsorbs within the active site of the polymer [36] and that the drug adsorption process controlled by the diffusion step belongs to the physical adsorption [34].…”

“…In this work, a MIP selective for Sunitinib was prepared by precipitation polymerization and was then functionalized with Rhodamine 6G by a radical grafting procedure. SUT, indeed, represents one of the most widely used tyrosine kinase inhibitors (TKI) for the treatment of several kinds of cancer [9,10]. This therapeutic agent has been approved by the US Food and Drug Administration (FDA) for the management of gastrointestinal stromal tumor (GIST), pancreatic neuroendocrine tumor (PNT), and renal-cell carcinoma (RCC).…”

Synthesis and Characterization of Multifunctional Interpenetrating Polymer and Its Applications in Protein Adsorption and Magnetite Loading

“…Xiuyu Jiang et al, employed graft copolymers as a water‐soluble coating for building superparamagnetic iron oxide nanoparticles, however, the side chains retarded the growth of Fe 3 O 4 NPs by the shielding effect. Hariom Gupta et al, successfully synthesized dehydroascorbic acid (DHA) coated Fe 3 O 4 NPs by co‐precipitation, and the value of saturation magnetization decreased with the increase of DHA concentration in synthesis.…”

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

“…Among smTKIs, SUT, a second-generation drug, is a multi-targeted receptor TKI orally administered for the treatment of gastrointestinal stromal tumors, advanced renal cell carcinomas and progressive, well-differentiated pancreatic neuroendocrine tumors (Wu et al, 2014;Parisi et al, 2015b). SUT possesses anti-cancer and anti-angiogenic activities, due to the potent inhibition of vascular endothelial growth factor receptors (types 1-3), platelet derived growth factor receptor (a and b), as well as fms-like tyrosine kinase 3, stem-cell factor receptor, colony-stimulating factor receptor (type 1) and glial cell-line derived neurotrophic factor receptor (Izzedine et al, 2007;Papaetis & Syrigos, 2009).…”