Micelles self-assembled by 3-O-β-d-glucopyranosyl latycodigenin enhance cell membrane permeability, promote antibiotic pulmonary targeting and improve anti-infective efficacy

Abstract

Background Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task. Results In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-d-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. Conclusions GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.

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Advances in Separation, Biological Properties, and Structure–Activity Relationship of Triterpenoids Derived from Camellia oleifera Abel

“…With escalating demands for eco-friendly natural auxiliary substances, natural biosurfactants have attracted extensive attention. the potential of saponin surfactants in drug delivery systems has been extensively documented . On account of self-assembly, CoS can form complexes with drugs and contribute to drug delivery.…”

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“…Targeted drug delivery is an advantage of polymeric micelles over conventional pulmonary drug delivery carriers. Zhang et al [ 236 ] designed and constructed a versatile lung-targeting NP. The self-assembled micelles were based on their specific amphiphilic structure and comprised the duckweed seed secondary saponin element 3- O -β- d -glucopyranosyl lentil element 682 (GP-682).…”