Formulation Optimization and Stability of Polymyxin B Based on Sodium Deoxycholate Sulfate Micelles

Abstract

Polymyxin B (PMB) and sodium deoxycholate sulfate (SDCS) ratios were optimized. The self-assembly of PMB-SDCS was characterized using dynamic light scattering. Five different mole ratios of SDCS to PMB (5:1, 10:1, 15:1, 30:1, and 45:1) were prepared after optimization. FTIR and ¹H-NMR were employed to characterize PMB formulations. The chemical stability of PMB was quantified with tandem mass spectrometry. Both PMB and SDCS formed micelles at 14 and 8 μg/ml, respectively. At the critical micelle concentration (CMC), the hydrodynamic diameter of 213 nm was obtained. PMB had a positive charge (+6 mV) while SDCS had a negative charge (‒33 mV). Increasing in SDCS content decreased the charges from ‒6 to ‒25 mV. FTIR revealed H-bonding between PMB and SDCS. The NMR spectra confirmed that chemical shifts of PMB and SDCS did not change. The hydrodynamic size of PMB-SDCS was from 193 to 318 d.nm. Our results suggest that the lower mole ratios of SDCS (< 15:1) were able to stabilize PMB and released PMB within 30 min. Moreover, 5:1 mole ratio maintained the antimicrobial activity against Pseudomonas aeruginosa (MBC = 2 μg/ml). PMB-SDCS micelles of particular mole ratio is able to provide physical and chemical stability of PMB.

Keywords: Antimicrobial activity; Micelles; Polymyxins; Sodium deoxycholate sulfate; Stability.