Presentation description

Chronic rhinosinusitis (CRS) is an incurable inflammatory disease of the sinonasal cavity that affects approximately 31 million Americans annually. CRS is historically classified into two phenotypes, with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP), which are noncancerous tissues that form in the nose and sinus. Studies have implicated Toll-like receptor (TLR) signaling pathways in the development of CRSwNP and CRSsNP. Current treatments may alleviate CRS symptoms, but approximately 50% of patients remain unresponsive due to complex pathophysiology. GM-1111 is a synthetic glycosaminoglycan and TLR antagonist shown to reduce CRS-associated inflammation in mice via intranasal administration. Although GM-1111 has promising anti-inflammatory properties, its short half-life requires daily dosing, potentially leading to safety concerns with long-term treatment. We hypothesize that the development of a new drug delivery vehicle, capable of releasing GM-1111 systemically for a prolonged period, will lead to effective treatment of CRS. To address this, we will synthesize poly lactic-co-glycolic acid (PLGA) microparticles encapsulating GM-1111 using a water-in-oil-in-water emulsion method. We will analyze the encapsulation efficiency, size, morphology, zeta potential, and polydispersity of our GM-1111-PLGA microparticles. We will then implement various modifications to the synthesis method to achieve particles with higher encapsulation to alleviate CRS symptoms. Our preliminary results demonstrate that 80% GM-1111 encapsulation efficiency can be achieved with an average size of 13.2 ± 1.8 µm and polydisperisty of 0.238 ± 0.123 of PLGA microparticles. Future research will optimize these particles based on GM-1111 release, pharmacokinetics, and efficacy in mouse models of CRS.