Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction

The Potential Use of Antibiotics Against Helicobacter pylori Infection: Biopharmaceutical Implications

[EN] Helicobacter pylori (H. pylori) is a notorious, recalcitrant and silent germ, which can cause a variety of debilitating stomach diseases, including gastric and duodenal ulcers and gastric cancer. This microbe predominantly colonizes the mucosal layer of the human stomach and survives in the inhospitable gastric microenvironment, by adapting to this hostile milieu. In this review, we first discuss H. pylori colonization and invasion. Thereafter, we provide a survey of current curative options based on polypharmacy, looking at pharmacokinetics, pharmacodynamics and pharmaceutical microbiology concepts, in the battle against H. pylori infection.Miri, AH.; Kamankesh, M.; Llopis-Lorente, A.; Liu, C.; Wacker, MG.; Haririan, I.; Asadzadeh Aghdaei, H.... (2022). The Potential Use of Antibiotics Against Helicobacter pylori Infection: Biopharmaceutical Implications. Frontiers in Pharmacology. 13:1-16. https://doi.org/10.3389/fphar.2022.9171841161

Physico-Mechanical Analysis of Free Ethylcellulose FilmsPlasticized with Incremental Weight Percents of Dibutyl Sebacate: Ethylcellulose membranes plasticized with dibutyl sebacate

This research was conducted to investigate the physico-mechanical characteris-tics of the ethylcellulose-based coating membranes plasticized with different weightpercents of dibutyl sebacate. In this experiment, free thin polymer sheetings of thesample formulations, by incorporating incremental weight percents of the plasticizer,were prepared employing a revised casting method of delayed solvent evaporation,whereby similar flat specimens of standard dimensions were subjected to tensileloadings and extensions. The data were analyzed to fairly decide on a moderateconcentration of the plasticizer to provide a rationale explanation of a strong, hard,and tough structure among the specimens. The data revealed that 40% (w/w) of theester results in the toughest structure amongst the similar specimens of the seriesleading to an ultimate toughness of 3.31 mj/m3

Optimization of electrospinning parameters for producing silk fibroin/poly(ethylene oxide) nanofibers using D-optimal method

Despite the ease of the electrospinning process of synthetic polymers, the adjustment of several independent variables for natural ones is a complex procedure. In this work, the electrospinning parameters of silk fibroin (SF)/poly(ethylene oxide) (PEO) blends including tip-to-collector distance (X1), applied voltage (X2), flow rate (X3) and SF/PEO ratio (X4) were optimized using the D-optimal method. By considering the response surface plots and interaction graphs as well as observing the scanning electron microscopy (SEM) images, the optimized conditions were set as follows: X1 = 15 cm, X2 = 12 kV, X3 = 1.2 mL/h and X4 = 4. Accordingly, the electrospun SF/PEO nanofibrous sample with uniform morphology and an average diameter of 182 ± 55 nm was obtained

Release profile and stability evaluation of optimized chitosan/alginate nanoparticles as EGFR antisense vector

Ebrahim Azizi1,4, Alireza Namazi1, Ismaeil Haririan2,5, Shamileh Fouladdel1, Mohammad R Khoshayand3, Parisa Y Shotorbani6, Alireza Nomani1,7, Taraneh Gazori1,21Molecular Research Lab, Department of Pharmacology and Toxicology, 2Department of Pharmaceutics, 3Department of Food and Drug Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; 5Biomaterials Research Center (BRC) Tehran, Iran; 6Pharmaceutical Sciences Branch, Azad University, Tehran, Iran; 7Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranAbstract: Chitosan/alginate nanoparticles which had been optimized in our previous study using two different N/P ratios were chosen and their ability to release epidermal growth factor receptor (EGFR) antisense was investigated. In addition, the stability of these nanoparticles in aqueous medium and after freeze-drying was investigated. In the case of both N/P ratios (5, 25), nanoparticles started releasing EGFR antisense as soon as they were exposed to the medium and the release lasted for approximately 50 hours. Nanoparticle size, shape, zeta potential, and release profile did not show any significant change after the freeze-drying process (followed by reswelling). The nanoparticles were reswellable again after freeze-drying in phosphate buffer with a pH of 7.4 over a period of six hours. Agarose gel electrophoresis of the nanoparticles with the two different N/P ratios showed that these nanoparticles could protect EGFR antisense molecules for six hours.Keywords: chitosan/alginate nanoparticles, release profile, freeze-drying, agarose gel electrophoresi

Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

Alireza Nomani1,6, Ismaeil Haririan1,5, Ramin Rahimnia2,4, Shamileh Fouladdel2, Tarane Gazori1, Rassoul Dinarvand1, Yadollah Omidi3, Ebrahim Azizi2,41Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Molecular Research Lab, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; 5Biomaterials Research Center (BRC) Tehran, Iran; 6Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranAbstract: To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5’-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity.Keywords: poly(amido amine) dendrimer, PAMAM, cytotoxicity, cell uptake, antisense oligonucleotide, epidermal growth factor recepto