Micelles self-assembled by 3-O-β-D-glucopyranosyl latycodigenin enhances cell membrane permeability, promotes antibiotic pulmonary targeting and improves anti-infect efficacy

Abstract

Background: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. It exhibits significant advantages compared to traditional pulmonary drug delivery systems. However, developing a formulation for each drug is a time-consuming and laborious task. Results: The present study designed and constructed a universal lung-targeting nanoparticle. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. After optimization, the GP-682 micelles obtained a stable zeta potential with a particle size between 60 to 90 nm, and the CMC value was approximately 42.3 μg/mL. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro . The results were visualized using fluorescent dye tracing, transmission electron microscopy observation and a lactate dehydrogenase releasing assay. The benefits enhanced the distribution of levofloxacin in mouse lung tissue and reduced the overdosing of antibiotic. Pseudomonas aeruginosa PA 14 strain-induced acute lung injury mice model demonstrated that preinjection of GP-682 micelles followed by antibiotic administration produced a higher survival rate and anti-infection efficacy in vivo , which included a reduction in pulmonary injury, bacterial invasion and the expression of cytokines compared to treatment with levofloxacin alone. Conclusions: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system to increase the use of antibiotic and provide a new option for antibiotic resistance and lung-targeting therapy.