Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

Elham Abdelmonem Mohamed,1 Irhan Ibrahim Abu Hashim,1 Rehab Mohammad Yusif,1,2 Ahmed Abdel Aziz Shaaban,3 Ahmed Ramadan El-Sheakh,3 Mohammed Fawzy Hamed,4 Farid Abd Elreheem Badria5 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 4Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 5Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt Abstract: Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. Keywords: naringin, pluronic F68, polymeric micelles, in vitro cytotoxicity, antiulcer, antitumor activit

Physical mapping of ribosomal DNA and genome size in diploid and polyploid North African Calligonum species (Polygonaceae)

38 p., tablas, gráf.Most Calligonum species are desert plants, characteristic of the Saharan bioclimatic region. All species karyologically analyzed until present have the basic chromosome number x = 9 and comprise diploids, triploids and tetraploids. The Tunisian flora comprises diploid Calligonum arich and C. azel, of restricted distribution, and the tetraploid C. comosum with wider distribution. Analyses of their karyotypes and polyploidisation-linked rDNA changes by orcein staining, fluorochrome banding with chromomycin A3 and fluorescent in situ hybridisation with 5S and 26S ribosomal DNA probes have been performed. We report the chromosome number for Calligonum arich (2n = 18) as well as the diploid level for C. comosum for the first time. Chromosome counts have also verified the earlier described tetraploid cytotype (2n = 36) of C. comosum. A general pattern of six GC-rich bands as well as two 35S sites and four 5S sites is described for Calligonum species at the diploid level although there is intraspecific variation regarding the site number in a second type of C. comosum, with one pair of 35S rDNA sites and two pairs of 5S rDNA sites. The tetraploid cytotype of C. comosum has undergone locus loss and genome downsizing. Genome size assessments confirmed previous data. Nonetheless, statistically significant differences were found depending on the type of tissue used for estimation. Measurements from seeds had always larger values than from leaves. The presence of cytosolic compounds in leaves, interfering with DNA staining, is discussed as a possible cause of the differences.This work was supported by the Dirección General de Investigación Científica y Técnica, government of Spain (CGL2010-22234-C02-01/BOS and CGL2010-22234-C02-02/BOS) and the Generalitat de Catalunya, government of Catalonia (‘‘Ajuts a grups de recerca consolidats’’, 2009SGR0439). SG and OH benefitted from Juan de la Cierva postdoctoral contracts of the Ministry of Economy and Competitiveness, government of Spain.Peer reviewe