ABSTRACT
Polymeric micellar systems are emerging as a very important class of nanopharmaceuticals due to their ability to improve pharmacokinetics and biodistribution of chemotherapy drugs, as well as to reduce related systemic toxicities. While these nanosized delivery systems inherently benefit from passive targeting through the enhanced permeation and retention effect leading to increased accumulation in the tumor, additional active targeting can be achieved through surface modification of micelles with targeting groups specific for overexpressed receptors of tumor cells. In this project, nontoxic, biodegradable, and modularly tunable micellar delivery systems were generated using two types of dendron-polymer conjugates. Either an AB type dendron-polymer construct with 2K PEG or an ABA type dendron-polymer-dendron conjugate with 6K PEG based middle block was used as primary construct; along with an AB type dendron-polymer containing a cRGDfK targeting group to actively target cancer cells overexpressing αυß3/αυß5 integrins. A set of micelles encapsulating docetaxel, a widely employed chemotherapy drug, were prepared with varying feed ratios of primary construct and targeting group containing secondary construct. Critical micelle concentrations of all micellar systems were in the range of 10-6 M. DLS measurements indicated hydrodynamic size distributions varying between 170 to 200 nm. An increase in docetaxel release at acidic pH was observed for all micelles. Enhanced cellular internalization of Nile red doped micelles by MDA-MB-231 human breast cancer cells suggested that the most efficient uptake was observed with targeted micelles. In vitro cytotoxicity experiments on MDA-MB-231 breast cancer and A549 lung carcinoma cell lines showed improved toxicity for RGD containing micelles. For A549 cell line EC50 values of drug loaded micellar sets were in the range of 10-9 M whereas EC50 value of free docetaxel was around 10-10 M. For MDA-MB-231 cell line EC50 value of free docetaxel was 6 × 10-8 M similar to EC50 of nontargeted AB type docetaxel doped micellar constructs whereas the EC50 value of its targeted counterpart decreased to 5.5 × 10-9 M. Overall, in this comparative study, the targeting group containing micellar construct fabricated with a 2 kDa PEG based diblock dendron-polymer conjugate emerges as an attractive drug delivery vehicle due to the ease of synthesis, high stability of the micelles, and efficient targeting.
Subject(s)
Dendrimers/chemistry , Drug Design , A549 Cells , Cell Survival/drug effects , Dendrimers/toxicity , Drug Liberation , Humans , Hydrogen-Ion Concentration , Micelles , Models, Molecular , Molecular Conformation , Peptides, Cyclic/chemistry , Polyethylene Glycols/chemistryABSTRACT
A novel glycoside, hirsutusoide (1), characterized as 2-(o-hydroxyphenyl)-2-hydroxyethenyl-O-beta-glucopyranoside, was isolated from the endemic Acanthus hirsutus Boiss. In addition to compound 1, three known glycosides, luteolin-7-O-beta-D-glucuronide (2), beta-sitosterol-3-O-beta-D-glucopyranoside (3) and (2R)-2-O-beta-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (4), were also isolated. Compound 2 was the first report from this genus. Antimicrobial and antioxidant activity of the extracts and the novel compound were investigated by determining MIC (microg/mL) and IC50 (microg/mL) values, respectively.
Subject(s)
Acanthaceae/chemistry , Anti-Bacterial Agents/isolation & purification , Free Radical Scavengers/isolation & purification , Glycosides/isolation & purification , Phenols/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Nuclear Magnetic Resonance, Biomolecular , Optical Rotation , Phenols/chemistry , Phenols/pharmacology , Plant Components, Aerial/chemistry , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Superoxides/chemistryABSTRACT
The marcs of two red grape (V. vinifera L.) varieties (Bogazkere and Oküzgözü), grown in eastern Anatolia (Elazig), were evaluated for their fatty acid composition, and antioxidant and antibacterial activities. The hexane extracts of both varieties were found to contain linoleic, palmitic, stearic and oleic acids by GC-MS analyses. The major fatty acid (linoleic acid) was detected relatively as 57.13% in Oküzgözü and 59.07% in Bogazkere in methylated hexane extracts. In addition, myristic and palmitoleic acids were observed in Bogazkere as minor components. The free radical (DPPH) scavenging activity of Oküzgözü was higher than that of Bogazkere. The IC50 values were calculated as 403.0 +/- 7.8 microg/mL for Oküzgozü and 552.0 +/- 23.6 microg/mL for Bogazkere. The extracts were found to be effective on the four gram (+) and four gram (-) test bacteria, but not as good as standard antibiotic, gentamycine by MIC method.
Subject(s)
Anti-Bacterial Agents/analysis , Antioxidants/analysis , Fatty Acids/analysis , Vitis/chemistry , Biphenyl Compounds , Gas Chromatography-Mass Spectrometry , Hexanes , Inhibitory Concentration 50 , Picrates , TurkeyABSTRACT
Two flavonoid glycosides (compounds 1 and 3) of which one is reported for the first time and a methylinositol (compound 2) were isolated from the aerial parts of Ebenus haussknechtii (Leguminosae). The structures were established as quercetin-7-O-[alpha-L-rhamnopyranosyl(1 --> 6)-beta-D-galactopyranoside] (1), morin-3-O-[4-[5-(4-hydroxyphenyl)pentanoyl]-alpha-L-rhamnopyranosyl(1 --> 6)-beta-D-galactopyranosyl]-7-4'-di-O-methyleter (3), and methylinositol (2) on the basis of chemical and spectroscopic means. The antimicrobial activities of the extracts have also been examined.
