Enhancing biocompatibility and neuronal anti-inflammatory activity of polymyxin B through conjugation with gellan gum

Polymyxins, as strong antibiotics with high liposaccharide deactivation abilities, are rarely used as neuronal anti-inflammatory agent because of their high cytotoxicity. In this study, polymyxin B (PMB) was conjugated with deacylated gellan gum for the sustained release of PMB to reduce its cytotoxicity at high concentration without affecting the antibacterial and liposaccharide binding activities. For the conjugate of original PMB/GN ratio of 1.0 (GPC), the conjugating rate was 96.40%, and the releasing ratio of PMB was 30.12% within 60 h. The FT-IR spectra of GPC indicated that the amino groups of PMB were covalently bonded with the COOH groups of gellan and other PMB molecules. Most GPCs were micelle shaped regardless of whether they were under dry conditions or in an aqueous solution. The inhibition zones of PMB against Escherichia coli and Pseudomonas aeruginosa were small, but the half maximal inhibitory concentration value against BV-2 cells increased from 15.63 μg/mL to 2000.00 μg/mL after conjugation. GPC can also effectively depress the liposaccharide-stimulated overexpression of cytotoxic nitric oxide by BV-2 cells. This study revealed the possibility of using polymyxins for neuronal anti-inflammation and that this gellan/PMB conjugate can potentially be applied to wound healing and implants.