The global submucosal injection solution market is estimated to be around $3 billion according to the incidenceand prevalence rates of medical diagnoses known to be associated with endoscopic mucosalresection/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 (AriesPharmaceuticals, Inc), OriseTM Gel (Boston Scientific), and EverliftTM (GI supply) are approved by FDA in theUnited States. These products are limited either by the inconsistent submucosal lift duration in preclinical andclinical settings or by their unsatisfactory injectability. Also, none of the products are able to address the bleedingproblem, one of the most common complications for EMR/ESD. The primary goal of the Phase I proposal is todevelop Aleo BME's proprietary multifunctional submucosal injection agent (Aleo BMESolution) that can facilitatethe safe surgical removal of gastrointestinal neoplasms via EMR/ESD, and enable post-surgical bleedingmanagement. Aleo BMESolution is a mixed fluid gel composition mainly composed of sodium alginate (SA) asthe gelling component, calcium-binding oligomer as the key modifier, and calcium ions as the crosslinker. Thenovelty lies in its design strategy in which a unique combination of a fluid gel concept borrowed from the foodindustry and a competitive binding mechanism via the introduction of a calcium-binding modifier was adopted tosimultaneously achieve low injection pressure for relatively high viscosity solutions and much-improvedhemostatic property. The Rigor of The Prior Research of the proposal is strongly supported by our preliminarydata, 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 oligomericmodifiers into alginate fluid gels significantly reduces the injection pressure of the system even at elevatedcalcium concentrations; 3) After injection into the confined submucosal space, a thickened hydrogel cushion isformed; 4) After resection, the residual of thickened fluid gels form a stable protective sealant (dressing) on thewound. 5) The addition of calcium-binding oligomeric modifiers makes it possible to make the shear-thinningmucoadhesive/mucoprotective fluid gels with elevated concentrations of alginate and calcium whichsynergistically contribute to the much-needed hemostaic properties of Aleo BMESolution. The expectedoutcome of this proposal is that we will develop an all-in-one multifunctional submucosal injection agent withsuperior performance over the existing products, such as desirable injection pressure, prolonged submucosallife, preferred rheological properties and shelf life, excellent biocompatibility, and unparalleled hemostaticfunction, to address ever-increasing needs in the underserved EMR/ESD injection solution market.
Public Health Relevance Statement: Project Narrative Submucosal injection of an agent to effectively separate the diseased gastrointestinal lesions from the underlying tissues is essential for successful endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) procedures. The primary goal of the SBIR Phase I proposal is to develop a 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.
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