Choline based polymethacrylate matrix with pharmaceutical cations as co-delivery system for antibacterial and anti-inflammatory combined therapy

Abstract

Anionic drugs, i.e. salicylate (Sal−) and sulfacetamide (Sfc−) were chosen as counterions in trimethylammonium based poly(meth)acrylates. These ionic systems with amphiphilic properties were used to form polymeric systems for dual drug delivery by loading of nonionic pharmaceutics like immunosuppressant quercetin (QUE), anti-inflammatory indomethacin (IMC) and antibiotic erythromycin (ERY). The latter one was loaded with high efficiency (>60%), whereas poorer loading efficiency was obtained for aromatic compounds (<10%) because of strong repulsing effect with ionic moieties in polymer matrix. Coordinating and polar properties of anions as the additional factors in drug-polymer affinity can be applied to adjust the drug loading and release. The polymer particles resulted in aqueous solutions were characterized by hydrodynamic diameters (70–430 nm) and zeta potentials (20–65 mV) indicating specific multifactor action/contraction of drug delivery system (DDS) components. The release profiles of both type drugs demonstrated typical diffusion process with burst effect during initial 2 h, and then it slowed down for next 80 h. The release rate of bioactive anions in the dual system was not affected by the presence of nonionic drug showing comparable kinetics profile with the analogical single drug system carrying ionic drug. The most promising Sal-based and ERY-loaded polymer system was able to release ~60% of ionic drug (via exchange with phosphate anions in buffer solution) and ~70% of nonionic drug. The biological studies on the proposed polymeric systems were conducted indicating no toxic activity against human cells (NHDF and BEAS-2B), no gene expression for anti-inflammatory interleukins IL6 and IL8 as well as the antibacterial activity was observed against E. coli.