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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), characterized by uncontrolled lung inflammation, is one of the most devastating diseases with high morbidity and mortality. As the first line of defense system, macrophages play a crucial role in the pathogenesis of ALI/ARDS. Therefore, it has great potential to selectively target M1 macrophages to improve the therapeutic effect of anti-inflammatory drugs. L-arginine plays a key role in regulating the immune function of macrophages. The receptors mediating L-arginine uptake are highly expressed on the surface of M1-type macrophages. In this study, we designed an L-arginine-modified liposome for aerosol inhalation to target M1 macrophages in the lung, and the anti-inflammatory drug curcumin was encapsulated in liposomes as model drug. Compared with unmodified curcumin liposome (Cur-Lip), L-arginine functionalized Cur-Lip (Arg-Cur-Lip) exhibited higher uptake by M1 macrophages in vitro and higher accumulation in inflamed lungs in vivo. Furthermore, Arg-Cur-Lip showed more potent therapeutic effects in LPS-induced RAW 264.7 cells and the rat model of ALI. Overall, these findings indicate that L-arginine-modified liposomes have great potential to enhance curcumin treatment of ALI/ARDS by targeting M1 macrophages, which may provide an option for the treatment of acute lung inflammatory diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome and middle east respiratory syndrome.

Oral administration is the most preferred route for drug administration in clinic. However, due to unsatisfactory physicochemical properties of drugs and various physiological barriers, the oral bioavailability of most poorly water-soluble and macromolecules drugs is low and the therapeutic effect is unsatisfactory. Ionic liquids (ILs), molten salts with unique properties, show amazing potential for oral delivery. In addition to being able to form active pharmaceutical ingredients based ILs (API-ILs) to overcome drug solubility and polymorphism issues, ILs have also been used to enhance the solubility of poorly soluble drugs, enhance drug stability in the gastrointestinal environment, improve drug permeability in intestinal mucus, and facilitate drug penetration across the intestinal epithelial barrier. Furthermore, ILs were attempted as formulation components to develop novel oral drug delivery systems. This review focus on the application progress of ILs in oral drug delivery and the mechanisms. The challenges and perspectives of the development of ILs-based oral delivery systems are also discussed. This article reviews the latest advances of ionic liquids for oral drug delivery, focusing on the application and related mechanisms of ionic liquids in improving the drug physicochemical properties and enhancing drug delivery across physiological barriers.

Salvianolic acids (SAL), the main bioactive component extracted from Salvia miltiorrhiza, is a natural product with a reported anti-pulmonary fibrosis (PF) effect. SAL is commonly administrated orally; however, it has a low oral bioavailability (less than 5%). The objective of this work was to develop a new dry powder inhalable formulation intended to facilitate the access of SAL to the target place. We prepared the new SAL powder formulation containing L-arginine and 2% of lecithin using the ball milling technique. L-arginine was used to regulate the strong acidity of the SAL solution, and lecithin was added to disperse the powder and improve the flowability. The resulting powder had a content in salvianolic acid B (SALB, the main active principle of SAL) of 66.67%, a particle size of less than 5 μm and a good flowability. In vivo fluorescence imaging showed that the powder could be successfully aerosolized and delivered to the lung. The acute lung irritation study proved that the presence of L-arginine improved the biocompatibility of the powder. Finally, according to the pharmacokinetic study, the new SAL powder formulation was found to significantly increase drug concentration in the lung and the bioavailability. In conclusion, the new dry powder inhalable formulation of SAL developed in this study could be a strategy to enhance the performance of SAL at the lung level. Graphical abstract.

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by interstitial inflammation and fibrosis. Salvianolic acid B (SAB) and sodium tanshinone IIA sulfonate (STS) are representative components in Salvia miltiorrhiza, which have been reported using in the treatment of PF. The aim of the study was to explain the role of inflammation in the process of PF and to investigate the effect of SAB and STS on inflammation and fibrosis in vitro. The results clearly indicated that lipopolysaccharide (LPS)-stimulated inflammatory response could induce fibroblast proliferation and fibroblast to myofibroblast transformation (FMT). Both SAB and STS significantly inhibited LPS-induced inflammation in vitro, including down-regulated the protein expression levels of IL-1β and TNF-α and the mRNA expression levels of IL1B and TNFA. Furthermore, both SAB and STS inhibited TGF-β1-induced the proliferation in MRC-5 cells and the overexpression of α-SMA and COL1α1, both the protein and mRNA levels. In conclusion, these results indicate that the inflammatory response is necessary for the development of PF, and the therapeutic effect of SAB and STS on PF may be related to anti-inflammatory and anti-fibrotic effects.

1,3,4,6-tetramethylpiperazine-2,5-dione was synthesized, and the crystal structure was characterized by single-crystal X-ray diffraction method, vibrational spectral measurements were obtained by Fourier transform infrared spectroscopy and Fourier transform Raman spectroscopy. The measurements agree well with the calculated geometrical structure and harmonic vibrational wavenumbers (usingab initio and density functional theory Becke’s three parameters hybrid method with the Lee, Yang, and Parr non-local functions methods with 6-311G and 6-311G** basis sets).

Transmembrane protein P-gp's overexpression at the drug-resistant cell membrane is the most important characteristic of multidrug resistance (MDR). Quercetin (QUE) can effectively suppress the function of P-gp to reverse MDR. This study uses QUE as the P-gp inhibitor andfilm-ultrasound technique with ammonium sulfate transmembrane gradient method to prepare long-circulating liposomes simultaneously encapsulating QUE and Adriamycin (doxorubicin) (AMD/DOX). The optimal conditions for the preparation of AMD_QUE_long-circulating liposomes (SLs) are as follows: hydrogenated soybean phospholipids (HSPC):cholesterol:DSPE-PEG 2000 = 73.07:24.36:2.57 mol/mol, QUE:HSPC = 1:20 mol/mol, AMD:HSPC = 1:7.9 w/w (NH4)2SO4 0.15 mol/L, drug loaded (AMD) at 55°C for 25 min). The average encapsulation efficiency of AMD and QUE was 97.49% and 95.50%, respectively. The average particle size is 85 nm (n = 3), and the average zeta potential is −14.9 mV. First, the pharmacokinetic study proved that codelivery liposomes enveloping QUE and AMD (AMD_QUE_SL) can obviously increase the blood concentration of AMD (Cmax: 140.50 ± 32.37 μg/mL) and extend the half-life period of AMD in plasma (t1/2:14.02 ± 1.54 h). Second, AMD_QUE_SL can obviously enhance the cell toxicity to AMD-resistant cell strains (HL-6/ADR and MCF-7/ADR), and the reverse effects on the resistance of HL-6/ADR and MCF-7/ADR is increased to 4.81-fold and 3.21-fold, respectively. Third, according to the in vivo pharmacodynamic study, the relative tumor volume and relative tumor growth of the AMD_QUE_SL group were the lowest. The inhibition rate of tumor growth of this group was the highest. It can be concluded that AMD_QUE_SL can effectively reverse MDR, lower cardiac toxicity of AMD in clinical treatment, and improve the clinical treatment effect of AMD.