Multifunctional injectable agent for endoscopic mucosal resection

Project Summary The global submucosal injection solution market is estimated to be around $3 billion according to the incidence and prevalence rates of medical diagnoses known to be associated with endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD), and the market is driven by the need to improve injectability and prolonged submucosal elevation. To date, only three submucosal lift solutions, EleviewTM (Aries Pharmaceuticals, Inc), OriseTM Gel (Boston Scientific), and EverliftTM (GI supply) are approved by FDA in the United States. These products are limited either by the inconsistent submucosal lift duration in preclinical and clinical settings or by their unsatisfactory injectability. Also, none of the products are able to address the bleeding problem, one of the most common complications for EMR/ESD. The primary goal of the Phase I proposal is to develop Aleo BME’s proprietary multifunctional submucosal injection agent (Aleo BMESolution) that can facilitate the safe surgical removal of gastrointestinal neoplasms via EMR/ESD, and enable post-surgical bleeding management. Aleo BMESolution is a mixed fluid gel composition mainly composed of sodium alginate (SA) as the gelling component, calcium-binding oligomer as the key modifier, and calcium ions as the crosslinker. The novelty lies in its design strategy in which a unique combination of a fluid gel concept borrowed from the food industry and a competitive binding mechanism via the introduction of a calcium-binding modifier was adopted to simultaneously achieve low injection pressure for relatively high viscosity solutions and much-improved hemostatic property. The Rigor of The Prior Research of the proposal is strongly supported by our preliminary data, including: 1) Aleo BMESolution is a shear-thinning alginate fluid gel that is a suspension of calcium- crosslinked gelled particles weakly held together via inter-particle interactions; 2) The tactic addition of oligomeric modifiers into alginate fluid gels significantly reduces the injection pressure of the system even at elevated calcium concentrations; 3) After injection into the confined submucosal space, a thickened hydrogel cushion is formed; 4) After resection, the residual of thickened fluid gels form a stable protective sealant (dressing) on the wound. 5) The addition of calcium-binding oligomeric modifiers makes it possible to make the shear-thinning mucoadhesive/mucoprotective fluid gels with elevated concentrations of alginate and calcium which synergistically contribute to the much-needed hemostaic properties of Aleo BMESolution. The expected outcome of this proposal is that we will develop an all-in-one multifunctional submucosal injection agent with superior performance over the existing products, such as desirable injection pressure, prolonged submucosal life, preferred rheological properties and shelf life, excellent biocompatibility, and unparalleled hemostatic function, to address ever-increasing needs in the underserved EMR/ESD injection solution market.