Glycyrrhetinic acid loaded in milk-derived extracellular vesicles for inhalation therapy of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and life-threatening lung disease for which treatment options are limited. Glycyrrhetinic acid (GA) is a triterpenoid with multiple biological effects, such as anti-inflammatory and anti-fibrotic properties. Herein, inhalable milk-derived extracellular vesicles (mEVs) encapsulating GA (mEVs@GA) were screened and evaluated for IPF treatment. The results indicated that the loading efficiency of GA in mEVs@GA was 8.65%. Therapeutic effects of inhalable mEVs@GA were investigated in vitro and in vivo. The mEVs@GA demonstrated superior anti-inflammatory effects on LPS-stimulated MHS cells. Furthermore, repeated noninvasive inhalation delivery of mEVs@GA in bleomycin-induced IPF mice could decrease the levels of transforming growth factors ß1 (TGF-ß1), Smad3 and inflammatory cytokines IL-6, IL-1ß and TNF-α. The mEVs@GA effectively diminished the development of fibrosis and improved pulmonary function in the IPF mice model at a quarter of the dose compared with the pirfenidone oral administration group. Additionally, compared to pirfenidone-loaded mEVs, mEVs@GA demonstrated superior efficacy at the same drug concentration in the pharmacodynamic study. Overall, inhaled mEVs@GA have the potential to serve as an effective therapeutic option in the treatment of IPF.

Enhanced Stability and Solidification of Volatile Eugenol by Cyclodextrin-Metal Organic Framework for Nasal Powder Delivery.

Eugenol (Eug) holds potential as a treatment for bacterial rhinosinusitis by nasal powder drug delivery. To stabilization and solidification of volatile Eug, herein, nasal inhalable γ-cyclodextrin metal-organic framework (γ-CD-MOF) was investigated as a carrier by gas-solid adsorption method. The results showed that the particle size of Eug loaded by γ-CD-MOF (Eug@γ-CD-MOF) distributed in the range of 10-150 µm well. In comparison to γ-CD and ß-CD-MOF, γ-CD-MOF has higher thermal stability to Eug. And the intermolecular interactions between Eug and the carriers were verified by characterizations and molecular docking. Based on the bionic human nasal cavity model, Eug@γ-CD-MOF had a high deposition distribution (90.07 ± 1.58%). Compared with free Eug, the retention time Eug@γ-CD-MOF in the nasal cavity was prolonged from 5 min to 60 min. In addition, the cell viability showed that Eug@γ-CD-MOF (Eug content range 3.125-200 µg/mL) was non-cytotoxic. And the encapsulation of γ-CD-MOF could not reduce the bacteriostatic effect of Eug. Therefore, the biocompatible γ-CD-MOF could be a potential and valuable carrier for nasal drug delivery to realize solidification and nasal therapeutic effects of volatile oils.

Rapid isolation of extracellular vesicles using covalent organic frameworks combined with microfluidic technique.

Extracellular vesicles (EVs) are nano-sized lipid-membrane vesicles involved in intercellular communication and reflecting the physiological and pathological processes of their parental cells. Rapid isolation of EVs with low cost is an essential precondition for downstream function exploration and clinical applications. In this work, we designed a novel EVs isolation device based on the boronated organic framework (BOF) coated recyclable microfluidic chip (named EVs-BD) to separate EVs from cell culture media. Using a reactive oxygen species responsive phenylboronic ester compound, the highly porous BOF with a pore size in the range of 10-300 nm was prepared by crosslinking γ-cyclodextrin metal-organic frameworks. A mussel-inspired polydopamine (PDA)/polyethyleneimine (PEI) coating was employed to pattern BOF on the PDMS substrate of microfluidic channels. The EVs-BD was demonstrated to offer distinct advantages over the traditional ultracentrifugation method, such as operation simplicity and safety, reduced time and expense, and low expertize requirements. All things considered, a novel approach of EV acquisition has been successfully developed, which can be customized easily to meet the requirements of various EV-relevant research.