Abstract
Here, we describe the preparation and characterisation of polyion complex (PIC) nanoparticles containing last resort antimicrobial polymyxin B (Pol-B). PIC nanoparticles were prepared with poly(styrene sulphonate) (PSS) as an inert component, across a range of degrees of polymerisation to evaluate the effect that multivalency of this electrolyte has on the stability and antimicrobial activity of these nanoparticles. Our results demonstrate that while nanoparticles prepared with longer polyelectrolytes are more stable under simulated physiological conditions, those prepared with shorter polyelectrolytes have a higher antimicrobial activity. Tailoring the degree of polymerisation and the ratio of the components we have been able to identify a formulation that shows a sustained inhibitory effect on the growth of P. aeruginosa and can reduce the number of viable colonies of this pathogen over 10,000 times more effectively than our previously reported formulation.
Highlights
We describe the preparation and characterisation of polyion complex (PIC) nanoparticles containing last resort antimicrobial polymyxin B (Pol-B)
Our results indicate that nanoparticles prepared with shorter poly(styrene sulphonate) (PSS) are less stable under simulated physiological conditions but result in significantly higher antimicrobial activities, and leads to the identification of a formulation that shows a sustained inhibitory effect on the growth of P. aeruginosa and that reduces the number of viable colonies of this pathogen more effectively than our previously reported formulation
We have recently reported the preparation of PIC nanoparticles via self-assembly of the cationic antibiotic polymyxin B (Pol-B) and the polyanion poly(styrene sulphonate) (PSS)[15]
Summary
We have recently reported the preparation of PIC nanoparticles via self-assembly of the cationic antibiotic polymyxin B (Pol-B) and the polyanion poly(styrene sulphonate) (PSS)[15]. Since the stability of PIC particles in solution strongly depends on the multivalency of their constitutive polyelectrolytes[3], we propose here that the complexation of Pol-B with shorter PSS would lead to less stable polyelectrolyte complexes with potentially faster Pol-B release profiles and higher antimicrobial activities. To test this hypothesis, we investigated the assembly of PIC nanoparticles from Pol-B and PSS with average molecular weights below 70 kDa. We selected commercial PSS sources of 30 and 15 kDa to test polymers with approximately half and a fourth of the Mw previously reported. Any attempt to remove loosely bound drug will result in the destabilisation of the system, for PIC particles like the ones reported here that
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