Xanthan gum and tamarind seed polysaccharide crosslinked metformin film: Potential against pollution-induced conjunctivitis and diabetes-induced elevated vitreous vascular endothelial growth factor.

Metformin (MET) is known to modulate pathways that are also activated by particulate matter 2.5 (PM2.5) for induction of conjunctivitis. It also reduces vascular endothelial growth factor (VEGF) expression, a significant reason for diabetic retinopathy. Despite the prophylactic effects of oral MET, topical use is necessary to achieve the higher levels needed for therapeutic efficacy. So, tamarind seed polysaccharide (TSP) was crosslinked with xanthan gum (XG) to provide a high polar surface area to load higher MET (5 mg/6 mm). Citric acid (CA) further crosslinked the matrix, improving the mechanical strength of the film and controlling release (∼70 h) without any burst effect. It was biocompatible with high precorneal residence (12h) and significantly (P < 0.05) reduced conjunctivitis in vivo (2.5 mg/3 mm; q.d.), unlike the solution with an equivalent dose (2.5 mg/mL; t.i.d) and prior insert (MET-TSP; q.d.) with a lower dose (1.5 mg/3 mm). Moreover, it ensured a higher MET level in the vitreous and effectively reduced the diabetes-induced elevated VEGF. These findings highlight that TSP-XG crosslinking can achieve higher loading of polar drugs like MET while maintaining a low drug-to-excipient ratio and ensuring adequate biocompatibility, ocular residence, controlled release, and stability for ocular application.