Delivery of theophylline as dry powder for inhalation

Theophylline(TP)is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects.This study aims to improve asthma treatment by creating a dry powder inhalable(DPI)formulation of TP to be delivered directly to the lung,avoiding the side effects associated with conventional oral delivery.The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy,laser diffraction,thermal analysis and dynamic vapour sorption.Furthermore,aerosol performance was assessed using the Multi Stage Liquid Impinger(MSLI).In addition,a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells.Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery.The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70±2.59%(P<0.05)for the TP formulation containing 1.0%(w/w)sodium stearate,the most efficient for aerosolisation.Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI,results demonstrated that 56.14±7.62%of the total TP deposited(13.07±1.69μg)was transported across the Calu-3 monolayer over 180 min following deposition,while 37.05±12.62%of the deposited TP was retained in the cells.This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity.A DPI formulation of TP was developed that was shown to be suitable for inhalation.

Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer

Cancer-associated fibroblasts(CAFs)are the vital constituent of the tumor microenvironment,and in communication with other cells,they contribute to tumor progression and metastasis.Fibroblasts are the proposed origin of CAFs,which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing.Although various studies have identified different subpopulations of CAFs in lung cancer,the heterogeneity of CAFs,particularly in lung cancer,and their potential as a therapeutic target remain largely unknown.Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features,their pro-or anti-tumorigenic properties may depend on various conditions and cell origins.The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer.Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression,suggesting that subpopulations of CAFs may exert opposing functions in cancer progression.Therefore,it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function.The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancerpromoting CAF subsets in lung cancer.