Poloxamer407/gellan gum-based in situ hydrogels for ocular co-delivery of antibiotics and corticosteroids

Abstract

To tackle the ocular inflammation and infection, we developed a Poloxamer 407 (PM)-gellan gum (GG)-based (PM-GG) in situ hydrogels containing dexamethasone (DEX)-loaded chitosan (CS) nanoparticles (DEX-CSNPs), neomycin sulfate (NMS), and polymixin b sulfate (PMB). Such a hybrid hydrogel was developed for the localized co-delivery of antibiotics and corticosteroids. The physicochemical properties of DEX-CSNPs (i.e., size: 286 nm, zeta potential: 20.3, entrapment efficiency: 29.4 %, and loading capacity: 6.5 %) displayed their suitability for ocular applications. To have the desired mucoadhesive hydrogel system, various combinations of GG and PM were examined. The mixture of 0.1 % GG and 16.5 % PM showed a significant increase in viscosity compared to 16.5 % PM alone. The porous structure of hydrogels was also observed from the SEM analysis, in which the pore size of PM gel decreased with the addition of GG. The PM-GG hydrogels reached less swelling percentage compared to PM hydrogels due to the higher viscosity of PM-GG hydrogels. Additionally, drug release studies and the antimicrobial test showed prolonged and effective release of drugs from PM-GG in situ hydrogels. Cell viability assay showed that the optimized formulation is well tolerated by cells with no obvious toxic effect on human umbilical vein endothelial cells (HUVECs). Collectively, the designed formulation is proposed as a novel drug delivery system for ocular codelivery of antibiotics and corticosteroids.

Keywords: Chitosan nanoparticles; Gellan gum; In situ hydrogels; Ocular delivery; Poloxamer.