Enhancing Quercetin's Potential: A Nanoliposome Delivery System for High Altitude Pulmonary Edema

Area of Science:

• Pharmacology and Nanotechnology
• Respiratory Medicine
• Molecular Biology

Background:

• Quercetin (QU) has potential for preventing high-altitude pulmonary edema (HAPE), but its low oral bioavailability limits therapeutic efficacy.
• Developing novel drug delivery systems is crucial to enhance quercetin's bioavailability and therapeutic outcomes for HAPE.

Purpose of the Study:

• To develop quercetin-loaded nanoliposomes (QUL) to improve the oral bioavailability of quercetin (QU).
• To evaluate the efficacy of QU and QUL in preventing HAPE and elucidate the underlying molecular mechanisms.

Main Methods:

• Quercetin nanoliposomes (QUL) were prepared using the thin-film hydration method.
• Characterization included morphology, particle size, polydispersity index, drug loading, and in vitro release studies.
• An LC-MS/MS method was developed for quantifying QU and QUL in rat plasma; in vitro and in vivo efficacy studies in a mouse HAPE model were conducted, alongside Western blotting and immunofluorescence for mechanistic analysis.

Main Results:

• QUL exhibited optimal nanoparticle characteristics (157.08±1.215 nm size, 0.204±0.012 PDI) and enhanced QU absorption (Tmax: 1.167±0.408h, Cmax: 0.585±0.032ug/mL).
• Both QU and QUL improved lung permeability, reduced mortality, and decreased lung water content in a mouse HAPE model.
• Mechanistic studies revealed inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation and migration via PI3K/AKT/VEGF and ROCK/HIF/TRPC signaling pathways.

Conclusions:

• Quercetin effectively reduces lung water content by modulating key signaling pathways, indicating its therapeutic potential for HAPE.
• Quercetin-loaded nanoliposomes significantly improve quercetin's oral bioavailability, thereby enhancing its therapeutic efficacy in managing HAPE.