Cytotoxic effect and mechanism inducing cell death of alpha-mangostin liposomes in various human carcinoma and normal cells
ANTI-CANCER DRUGS
Authors: Benjakul, Ruthairat; Kongkaneramit, Lalana; Sarisuta, Narong; Moongkarndi, Primchanien; Mueller-Goymann, Christel C.
Abstract
The aims of this study were to develop -mangostin liposomes as well as to evaluate their physicochemical properties and cytotoxic activity. -Mangostin liposomes were prepared using the reverse-phase evaporation method with lipid composition of phosphatidylcholine to cholesterol at 7:3 molar ratios; their physicochemical properties and antiproliferative activity were assessed using an MTT assay in four human carcinoma cells [that is, human lung epithelial carcinoma (Calu-3), human colon carcinoma (HT-29), human breast carcinoma (MCF-7), and human colon carcinoma (Caco-2) cells], and two human normal cells [that is, human dermal fibroblasts (HDF) and human adult low-calcium elevated temperature (HaCaT) keratinocytes]. Determinations of morphological changes and oligonucleosomal DNA fragments were also carried out. The liposomal dispersions obtained were unilamellar vesicles as confirmed by cryotransmission and freeze-fracture electron microscopy with a particle size of 114nm and a potential of -2.56mV. The P-31-NMR spectra showed that -mangostin molecules orientated in the phospholipid bilayer membrane. The -mangostin could appreciably be entrapped with an efficiency and loading of 81 and 4%, respectively. The antiproliferative activity of -mangostin liposomes in various cancer and normal cells showed a dose-dependent inhibition in all treated cell lines. The antiproliferative effect of -mangostin liposomes was found to be associated with apoptosis, with differences in sensitivity among the cell lines treated. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
Nanoparticle-mediated delivery of the antimicrobial peptide plectasin against Staphylococcus aureus in infected epithelial cells
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Authors: Water, Jorrit Jeroen; Smart, Simon; Franzyk, Henrik; Foged, Camilla; Nielsen, Hanne Morck
Abstract
A number of pathogenic bacterial strains, such as Staphylococcus aureus, are difficult to kill with conventional antibiotics due to intracellular persistence in host airway epithelium. Designing drug delivery systems to deliver potent antimicrobial peptides (AMPs) intracellularly to the airway epithelial cells might thus be a promising approach to combat such infections. In this work, plectasin, which is a cationic AMP of the defensin class, was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles using the double emulsion solvent evaporation method. The nanoparticles displayed a high plectasin encapsulation efficiency (71-90%) and mediated release of the peptide over 24 h. The antimicrobial efficacy of the peptide-loaded nanoparticles was investigated using bronchial epithelial Calu-3 cell monolayers infected with S. aureus. The plectasin-loaded nanoparticles displayed improved efficacy as compared to non-encapsulated plectasin, while the eukaryotic cell viability was unaffected at the assayed concentrations. Further, the subcellular localization of the nanoparticles was assessed in different relevant cell lines. The nanoparticles were distributed in punctuate patterns intracellularly in Calu-3 epithelial cells and in THP-1 macrophages, whereas A549 epithelial cells did not show significant uptake of the nanoparticles. Overall, encapsulation of plectasin into PLGA-based nanoparticles appears to be a viable strategy to improve the efficacy of plectasin against infections in epithelial tissues. (C) 2015 Elsevier B.V. All rights reserved.