DescriptionBacterial infections are prevalent in cystic fibrosis patients and can result in a number of life-threatening complications including respiratory failure which is the leading cause of morbidity in this population. Standard antibiotic treatment is ineffective and requires high and frequent dosing due to the development of bacterial biofilms which serve as a protective barrier limiting the amount of drug that reaches the bacteria embedded inside. Furthermore, due to the vast amount of potential genetic mutations that can result in this disease, a cure has been difficult to develop.
To combat the bacterial infections, numerous nanoparticle formulations were created containing cationic antimicrobial peptides (CAP), either polymyxin B (PB) or tobramycin (TB), that are encapsulated in different polyelectrolyte surfactants (PS) that consists of PMAA, poly(methacrylic acid) or PPAA, poly(propylacrylic acid), grafted with varying percentages of Jeffamine, a polyethylene glycol (PEG) based polymer. The PS-CAP nanoparticles are hypothesized to increase circulation time of the antibiotic, assist in controlled release of the drug, and enhance membrane penetration allowing more effective delivery of the antimicrobial peptide to the targeted bacteria. In this work, the physical characteristics and antibacterial properties of the nanoformulations were investigated.
Sizing measurements were performed indicating an average ideal hydrodynamic radius of approximately less than 200 nm across all formulations. Several studies were then further conducted to test the antibacterial activity of the nanomedicine. The first study, a minimum inhibitory concentration (MIC) assay, tested the ability of the nanoparticles to inhibit growth of planktonic bacteria in media. The second study, a minimum biofilm eradication concentration (MBEC) assay was performed to determine the effectiveness of the nanoformulations in eradicating bacteria embedded inside bacterial biofilm. The final study, a pretreatment assay, involved exposing bacterial biofilm to a set concentration of PS before adding standard antibiotic treatment to determine if the polymer has inherent anti-biofilm or antibacterial properties.
Although studies failed to demonstrate a significant reduction in MBEC compared to the standard treatment across all formulations, MIC data indicated that PMAA 10%J in conjunction with either PB or TB had substantially decreased the lowest inhibiting concentration for all samples tested. Furthermore, the pretreatment study indicated that exposing PMAA 10%J to bacterial biofilm before adding PB has a significant effect in lowering the necessary concentration needed to eradicate the bacteria embedded inside. Based on these results, nanoformulations consisting of PMAA 10%J demonstrated the most significant reduction in bacterial activity.