ABSTRACT
Objectives: The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. Methods: The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). Results: Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 - 256.80-fold. Linear correlation analysis of terpenes' cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. Conclusion: cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.
ABSTRACT
The inherent limitations, including serious side-effects and drug resistance, of current chemotherapies necessitate the search for alternative treatments especially for lung cancer. Herein, the anticancer activity of colicin N, bacteria-produced antibiotic peptide, was investigated in various human lung cancer cells. After 24 h of treatment, colicin N at 5-15 µM selectively caused cytotoxicity detected by MTT assay in human lung cancer H460, H292 and H23 cells with no noticeable cell death in human dermal papilla DPCs cells. Flow cytometry analysis of annexin V-FITC/propidium iodide indicated that colicin N primarily induced apoptosis in human lung cancer cells. The activation of extrinsic apoptosis evidenced with the reduction of c-FLIP and caspase-8, as well as the modulation of intrinsic apoptosis signaling proteins including Bax and Mcl-1 were observed via Western blot analysis in lung cancer cells cultured with colicin N (10-15 µM) for 12 h. Moreover, 5-15 µM of colicin N down-regulated the expression of activated Akt (p-Akt) and its upstream survival molecules, integrin ß1 and αV in human lung cancer cells. Taken together, colicin N exhibits selective anticancer activity associated with suppression of integrin-modulated survival which potentiate the development of a novel therapy with high safety profile for treatment of human lung cancer.
