Nebulization of polyelectrolyte surfactant nanomedicine for treatment of lung bacterial infections
Creators: name: Razouk, Ingy
Publisher: name: No Publisher Supplied
Year: 2023

description: Cystic fibrosis (CF) is a genetic disease in which mucus secretion and clearance are dysregulated. In addition to direct effects on pulmonary function, the presence of thick, sticky mucus in the lungs provides a haven for infection by a number of species, among which Pseudomonas aeruginosa, a gram-negative bacterium, is the most common in adults (2). The presence of bacteria induces persistent inflammation in the lungs that may lead to respiratory function difficulty and eventually failure (2). The treatment for cystic fibrosis lung infections involves pulmonary or oral antibiotics, but unfortunately, the bacteria are often not eradicated, form strong biofilms, and eventually develop resistance to many antibiotics (2). For these reasons, new formulations are needed to assist in drug efficacy and preventing or overcoming resistance (3). Toward this end, nanoformulations of antibiotics have been developed to improve treatment of infections. The advantages of nanosystems allow for sustained release, limited systemic toxicity, and improved mucus penetration (3). Nebulizer therapy delivers active treatment directly to the respiratory system. While nebulizing solutions assists in drug delivery, aggregation has emerged as a major issue for peptide-based therapeutics, leading to loss of efficacy, altered pharmacokinetics, reduced stability and product shelf life, and induction of unwanted immunogenicity (10). To combat particle size aggregation, excipients, such as mannitol and glucose, have been observed and measured for particle size.In this work, to enhance drug delivery in the context of cystic fibrosis lung infections, nanoparticle antibiotic solutions were formulated and analyzed. Grafted polyelectrolytes, composed of poly (methacrylic acid) and Jeffamine, a polyethylene glycol (PEG) based polymer, were combined with cationic antimicrobial peptides (CAP) or tobramycin (TB). Excipients were also introduced, as they are hypothesized to assist in controlled release of the drug, decrease aggregation, enhance targeted drug delivery to the lungs through inhaled treatments, and increase efficacy in inhibiting bacterial growth. In this study, physical characteristics and antimicrobial properties of the nanoparticle antibiotic solutions were analyzed at different timepoints. Particle sizes were analyzed to average less than 200 nm for sample readings at the initial timepoint and nebulized after 24 hours of sitting at room temperature. The radius for nebulized samples after 24 hours at room temperature was less than 500 nm. However, there was no significant difference in particle size after adding excipients mannitol and glucose. A minimal inhibitory concentration (MIC) assay was performed to test the antimicrobial activity for the nanoparticle solutions. Although the study failed to show a significant decrease in MIC compared to the standard antibiotic solution, the data showed comparable results. The nanoparticle antibiotic solution performed equally to the control antibiotic solution. The nebulized nanoparticle antibiotic solution had a greater MIC value than non-nebulized. Based on these results, nanoparticle antibiotic solutions maintain the ability to inhibit bacterial growth following nebulization.