Effects of inhalable microparticle of flower of Lonicera japonica in a mouse model of COPD

Yang-Chun Park; Mirim Jin; Seung-Hyung Kim; Min-Hee Kim; Uk Namgung; Yoon Yeo

doi:10.1016/j.jep.2013.10.013

Effects of inhalable microparticle of flower of Lonicera japonica in a mouse model of COPD

J Ethnopharmacol. 2014;151(1):123-30. doi: 10.1016/j.jep.2013.10.013. Epub 2013 Nov 5.

Authors

Yang-Chun Park¹, Mirim Jin¹, Seung-Hyung Kim¹, Min-Hee Kim¹, Uk Namgung¹, Yoon Yeo²

Affiliations

¹ College of Oriental Medicine, Daejeon University, 96-3 Yongwun-dong, Daejeon 300-716, South Korea; East-West Biological Science Institute, Daejeon University, 96-3 Yongwun-dong, Daejeon 300-716, South Korea.
² College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: [email protected].

PMID: 24211495
DOI: 10.1016/j.jep.2013.10.013

Abstract

Ethnopharmacological relevance: Flower of Lonicera japonica (FLJ) is a traditional herbal medicine widely used in East Asia as an anti-inflammatory and anti-oxidative agent. The purpose of this study is to develop an inhalable powder formulation of FLJ and to evaluate its biological effects in a mouse model of chronic obstructive pulmonary disease (COPD).

Methods: Inhalable dry powder containing FLJ was produced by spray-drying with leucine as an excipient. Its aerodynamic properties and anti-inflammatory activities were evaluated using the Anderson cascade impactor (ACI) and a mouse model of COPD, respectively.

Results: FLJ microparticle (FLJmp) had a hollow spherical shape in electron microscopy and showed aerodynamic properties suitable for inhalation (fine particle fraction of 54.0 ± 4.68% and mass median aerodynamic diameter of 4.6 ± 0.34μm). FLJmp decreased TNF-α and IL-6 expression in RAW264.7 cells activated by lipopolysaccharide (LPS). In mice challenged with LPS and cigarette smoke solution (CSS) to develop COPD, FLJmp decreased the levels of TNF-α and IL-6 in bronchoalveolar fluidas well as the number of inflammatory cells including neutrophils in peripheral blood. In addition, FLJmp induced recovery of elastin and collagen distribution, reduction of caspase-3 expression in lung tissues of COPD mice.

Conclusions: Inhalational delivery of FLJ using a microparticle system is a promising strategy for the treatment of COPD.

Keywords: ACI; Anderson cascade impactor; BALF; COPD; CSS; FBS; FLJ; FLJ microparticle; FLJmp; FPF; H&E; HPLC; Inhalable microparticle; LPS; Lonicera japonica; M-T; MMAD; MMPs; Masson-trichrome; PAS; SD; Spray dryer; bronchoalveolar fluid; chronic obstructive pulmonary disease; cigarette smoke solution; fetal bovine serum; fine particle fraction; flower of Lonicera japonica; hematoxylin–eosin; high pressure liquid chromatography; lipopolysaccharide; mass median aerodynamic diameter; matrix metalloproteinases; periodic acid-Schiff; standard deviation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Chromatography, High Pressure Liquid
Flowers / chemistry*
Gene Expression Regulation / drug effects
Interleukin-6 / genetics
Interleukin-6 / metabolism
Lonicera / chemistry*
Macrophages / drug effects
Macrophages / metabolism
Male
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Particle Size*
Powders / therapeutic use*
Pulmonary Disease, Chronic Obstructive / drug therapy*
Respiratory Therapy
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-6
Powders
Tumor Necrosis Factor-alpha