In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization

Abstract

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.

Polymeric materials for embolic and chemoembolic applications

“…A series of studies identifying an optimal SELP formulation for embolization were conducted (Fig. 4) [11]. Two SELP compositions were tested, i.e., SELP-47K and SELP-815K.…”

“…Both hematoxylin/eosin (H&E) and immunochemistry (IHC) staining methods were used to identify the solidified embolic. Figures modified from [11]. …”

“…To address these concerns, degradable materials composed of chitosan derivatives, for example, are being designed for synthesis of microspheres with predictable degradation rates [10]. More recently, biodegradable recombinant silk-elastinlike block copolymers have been used as a liquid embolic [11]. This review highlights these and a series of other embolic materials, first exploring clinical applications followed by material details including physical and mechanical properties, advantages, and disadvantages followed by a discussion of future directions in this field.…”

Antibiotic free selection for the high level biosynthesis of a silk-elastin-like protein

“…Materials and biomaterials based on proteins have attracted much attention in recent years due to their unique mechanical and biological properties1234 which rival those of synthetic polymers and lend them to numerous applications in a wide range of areas567891011. These protein based polymers (PBPs) are expected to substitute synthetic polymers in many applications as they offer the advantages of being monodisperse, biodegradable, biocompatible and more environmentally friendly123.…”

“…Furthermore, the genetically encoded template-based synthesis of these polymers provides for precise control of their design and the fabrication of novel customised biopolymers tailored for a particular application. Some potential applications include drug delivery, tissue engineering and as constituents of implanted medical devices, as well as surgical applications such as soft tissue augmentation and bone repair567891011.…”