Polyzwitterionic Nanogels for Controlled and Sustained Release of Bicarbonate Anions for Treatment of Metabolic Acidosis

Despite the reported evidence of deleterious effects of metabolic acidosis (MA), the development of advanced treatment options for this critical condition has not been explored much. Based on fundamental research and clinical trials, correcting MA with bicarbonate anions has a vast array of potential benefits. To achieve this objective, herein, we report on cytocompatible, charged polyzwitterionic nanogels (PZNGs) that can efficiently fix and release bicarbonate anions by a controlled and sustained mechanism. Three different PZNGs were synthesized using free radical polymerization with Pluronic F-127 as a non-ionic surfactant. From dynamic light scattering analysis, the hydrodynamic sizes (Dh) were found to be 68 +/- 6, 120 +/- 3, and 97 +/- 9 nm for PZNG-1, PZNG-2, and PZNG-3, respectively. The fixation of HCO3- on PZNGs was done either by direct reaction with NaHCO3 or by CO2 gas bubbling into a dispersion of PZNGs, and the maximum loading efficiency was found to be similar to 87-95%. Accelerated stability studies showed good stability for 30 days at 25 and 2-8 degrees C for the nanogels. The cytocompatibility results of the PZNGs from the MTT assay and the live-dead test confirm their non-toxicity, safety, and potential for various biomedical applications. The in vitro drug release profile revealed a sustained and controlled release pattern of HCO3- with a maximum of similar to 90% cumulative release in 168 h. The Korsmeyer-Peppas kinetic model suggests that the HCO3- anion release was regulated by diffusion of the anions and swelling of polymeric nanogels. In addition to the fixation and sustained release mechanisms described, the PZNGs reported here act as a simple and efficient carrier to deliver HCO3- anions for the treatment of MA with reduced complications.