Percutaneous transcatheter embolization procedures involve the selective occlusion of blood vessels. Occlusive agents, referred to as embolics, vary in material characteristics including chemical composition, mechanical properties, and the ability to concurrently deliver drugs. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives, in situ gelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackable in vivo. This article reviews commercially available materials used for embolization as well as polymeric materials that are under investigation.

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Hepatocellular carcinoma annually affects over 700,000 people worldwide and trends indicate increasing prevalence. Patients ineligible for surgery undergo loco-regional treatments such as transarterial chemoembolization (TACE) to selectively target tumoral blood supply. Using a microcatheter, chemotherapeutics are infused followed by an embolic agent, or the drug is encapsulated by the embolic moiety; simultaneously inducing stasis while delivering localized chemotherapy. Presently, several products are used, but no universally accepted system is promoted because very disparate limitations exist. The goal of this investigation was to design and develop in situ gelling recombinant silk-elastinlike protein polymers (SELPs) for TACE. Two SELP compositions, SELP-47K and SELP-815K, with varying lengths of silk and elastin blocks, were investigated to formulate a new embolic that was injectable through commercially available microcatheters. The goal was to develop a composition providing maximal permeation of tumor vasculature while exhibiting effective embolic activity. The SELPs evaluated remain soluble until reaching 37°C, when irreversible tran sition ensues forming a solid hydrogel network. SELP-815K formulated at 12% w/w with shear processing demonstrated acceptable rheological properties and clear embolic capability under flow conditions in vitro. A rabbit model showed feasibility of embolization in vivo allowing selective occlusion of lobar hepatic arterial branches.

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.

Silk-elastinlike protein polymers (SELPs) have been effectively used as controlled release matrices for the delivery of viruses for cancer gene therapy in preclinical models. However, the degradability of these polymers needs to be tuned for improved localized intratumoral gene delivery. Using recombinant techniques, systematic modifications in distinct regions of the polymer backbone, namely, within the elastin blocks, silk blocks, and adjacent to silk and elastin blocks, have been made to impart sensitivity to specific matrix metalloproteinases (MMPs) known to be overexpressed in the tumor environment. In this report we investigated the structure-function relationship of MMP-responsive SELPs for viral mediated gene therapy of head and neck cancer. These polymers showed significant degradation in vitro in the presence of MMPs. Their degradation rate was a function of the location of the MMP-responsive sequence in the polymer backbone when in hydrogel form. Treatment efficacy of the adenoviral vectors released from the MMP responsive SELP analogs in a xenograft mouse model of head and neck squamous cell carcinoma (HNSCC) was shown to be polymer structure dependent. These results demonstrate the tunable nature of MMP-responsive SELPs for localized matrix-mediated gene delivery.