ABSTRACT
Epilobium angustifolium L. is a medicinal plant well known for its anti-inflammatory, antibacterial, antioxidant, and anticancer properties related to its high polyphenols content. In the present study, we evaluated the antiproliferative properties of ethanolic extract of E. angustifolium (EAE) against normal human fibroblasts (HDF) and selected cancer cell lines, including melanoma (A375), breast (MCF7), colon (HT-29), lung (A549) and liver (HepG2). Next, bacterial cellulose (BC) membranes were applied as a matrix for the controlled delivery of the plant extract (BC-EAE) and characterized by thermogravimetry (TG), infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) images. In addition, EAE loading and kinetic release were defined. Finally, the anticancer activity of BC-EAE was evaluated against the HT-29 cell line, which presented the highest sensitivity to the tested plant extract (IC50 = 61.73 ± 6.42 µM). Our study confirmed the biocompatibility of empty BC and the dose and time-dependent cytotoxicity of the released EAE. The plant extract released from BC-2.5%EAE significantly reduced cell viability to 18.16% and 6.15% of the control values and increased number apoptotic/dead cells up to 37.53% and 66.90% after 48 and 72 h of treatment, respectively. In conclusion, our study has shown that BC membranes could be used as a carrier for the delivery of higher doses of anticancer compounds released in a sustained manner in the target tissue.
ABSTRACT
Bacterial cellulose membranes (BCs) are becoming useful as a drug delivery system to the skin. However, there are very few reports on their application of plant substances to the skin. Komagataeibacter xylinus was used for the production of bacterial cellulose (BC). The BC containing 5% and 10% ethanolic extract of Epilobium angustifolium (FEE) (BC-5%FEE and BC-10%FEE, respectively) were prepared. Their mechanical, structural, and antioxidant properties, as well as phenolic acid content, were evaluated. The bioavailability of BC-FESs using mouse L929 fibroblasts as model cells was tested. Moreover, In Vitro penetration through the pigskin of the selected phenolic acids contained in FEE and their accumulation in the skin after topical application of BC-FEEs was examined. The BC-FEEs were characterized by antioxidant activity. The BC-5% FEE showed relatively low toxicity to healthy mouse fibroblasts. Gallic acid (GA), chlorogenic acid (ChA), 3,4-dihydroxybenzoic acid (3,4-DHB), 4-hydroxybenzoic acid (4-HB), 3-hydroxybenzoic acid (3-HB), and caffeic acid (CA) found in FEE were also identified in the membranes. After topical application of the membranes to the pigskin penetration of some phenolic acid and other antioxidants through the skin as well as their accumulation in the skin was observed. The bacterial cellulose membrane loaded by plant extract may be an interesting solution for topical antioxidant delivery to the skin.
Subject(s)
Antioxidants/administration & dosage , Cellulose/chemistry , Epilobium/chemistry , Fibroblasts/drug effects , Plant Extracts/administration & dosage , Skin/drug effects , Administration, Topical , Animals , Bacteria/chemistry , Fibroblasts/metabolism , Mice , Skin/metabolism , SwineABSTRACT
Increasing multidrug resistance has led to renewed interest in phage-based therapy. A combination of the bacteriophages and antibiotics presents a promising approach enhancing the phage therapy effectiveness. First, phage candidates for therapy should be deeply characterized. Here we characterize the bacteriophage vB_AbaP_AGC01 that poses antibacterial activity against clinical Acinetobacter baumannii strains. Moreover, besides genomic and phenotypic analysis our study aims to analyze phage-antibiotic combination effectiveness with the use of ex vivo and in vivo models. The phage AGC01 efficiently adsorbs to A. baumannii cells and possesses a bacteriolytic lifecycle resulting in high production of progeny phages (317 ± 20 PFU × cell-1). The broad host range (50.27%, 93 out of 185 strains) against A. baumannii isolates and the inability of AGC01 to infect other bacterial species show its high specificity. Genomic analysis revealed a high similarity of the AGC01 genome sequence with that of the Friunavirus genus from a subfamily of Autographivirinae. The AGC01 is able to significantly reduce the A. baumannii cell count in a human heat-inactivated plasma blood model (HIP-B), both alone and in combination with antibiotics (gentamicin (GEN), ciprofloxacin (CIP), and meropenem (MER)). The synergistic action was observed when a combination of phage treatment with CIP or MER was used. The antimicrobial activity of AGC01 and phage-antibiotic combinations was confirmed using an in vivo larva model. This study shows the greatest increase in survival of G. mellonella larvae when the combination of phage (MOI = 1) and MER was used, which increased larval survival from 35% to 77%. Hence, AGC01 represents a novel candidate for phage therapy. Additionally, our study suggests that phages and antibiotics can act synergistically for greater antimicrobial effect when used as combination therapy.