Synthesis and characterization of glucocorticoid functionalized poly(N-vinyl pyrrolidone): a versatile prodrug for neural interface.
A poly(N-vinyl pyrrolidone)-based glucocorticoid prodrug was synthesized via a hydrazone linkage and characterized by (1)H NMR and UV-vis spectroscopy. pH sensitivity of drug release from the prodrug was observed under conditions mimicking inflammation-induced tissue acidosis. Multilayers of poly(acrylic acid)/prodrug were successfully deposited onto silicon substrates via hydrogen bond-driven layer-by-layer (LBL) assembly. The layers were destructible when incubated in physiological pH, which could be beneficial for biosensors such as neural electrodes. Bioactivity of the prodrug and its released free drug were studied with RAW264.7 macrophages in vitro, where inhibition of nitric oxide production was observed, suggesting the desired anti-inflammatory effect. Neural culture showed that both the prodrug and its precursor polymer were nontoxic to neurons and did not alter the ability of neurons to maintain neurite extensions, reassuring further application of this prodrug to mitigate inflammation at the neural interface. This system allows localized pharmacological interventions that deliver anti-inflammatory drugs based on the extent of inflammation without interfering with the electrical properties of the neural electrodes.
Cao
Yu
Y
Department of Materials Science and Engineering, The University of Tennessee, Knoxville, Tennessee 37996, USA.
He
Wei
W
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D005938:Glucocorticoids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011145:Polyvinyls / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D005938:Glucocorticoids; D011145:Polyvinyls; D011355:Prodrugs; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine)