Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

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Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin

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DPP-4 inhibitors and inhomogeneous static magnetic field, new therapeutic potentialities for the treatment of neuropatic pain and inflammation

1. A kutatómunka során két DPP-4 inhibitor vegyület, a sitagliptin és a vildagliptin fájdalomcsillapító és gyulladáscsökkentő hatását vizsgálatuk in vivo modellekben. 2. Vizsgáltuk az inhomogén sztatikus mágneses tér fájdalomcsillapító és gyulladáscsökkentő hatását in vivo modellekben. 3. A két gliptin vegyületről igazolódott, hogy különböző intenzitással, de mindkettő dózisfüggő módon gátolja a fájdalom kialakulását és a gyulladás kifejlődését. Ezen tulajdonságokat igazoltuk a CFA kezelést követően increasing hot plate és von Frey tesztekkel. A mustárolajjal kiváltott fülgyulladásban az ödéma nagyságának mérésével és a mieloperoxidáz aktivitáson keresztül a granulocita akkumuláció mérésével is bizonyítottuk a vegyületek gyulladásgátló képességét, ezekben a mérésekben a sitagliptin mutatkozott erősebbnek. 4. Mind a sitagliptin, mind a vildagliptin hatékonyan gátolta a capsaicinnel indukált plazmaextravazációt egér húgyhólyagban. Ebben a vizsgálatban a vildagliptin bizonyult hatékonyabb vegyületnek. 5. Az, hogy a két szer más-más kísérleti elrendezésben volt hangsúlyos azt sugallja, hogy hatásmechanizmusuk egymástól eltérő lehet. 6. A DPP-4 inhibitor vegyületek ígéretes gyógyszernek mutatkoztak a 2-es típusú diabétesz kezelésén túl új indikációs területen, a különböző gyulladásos betegségek kezelésében. 7. A napi 30 perces SMF expozíció a vér glükóz szintjét szignifikáns mértékben (p<0.05) csökkentette manifeszt diabéteszes állapot esetén, míg az egészséges állatok vér glükóz szintjét nem befolyásolta. 8. A napi 30 perces SMF expozíció nem volt hatással sem az egészséges, sem a diabéteszes állatok testtömegének alakulására. 9. A napi 30 perces SMF expozíció nem befolyásolta meggyőzően a fájdalomérzet alakulását sem egészséges, sem diabéteszes egerekben increasing hot plate teszttel mérve. 1. The purpose of the experimental work was to evaluate two DPP-4 inhibitors, sitagliptin and vildagliptin in the analgetic and antiinflammatory point of view in vivo. 2. We investigated the effects of the inhomogeneous static magnetic field form the analgetic and antiinflammatory point of view in vivo. 3. According to our results substances had different impact but both gliptins showed analgetic and antiinflamamtory effectiveness in a dose dependent manner. These properties had been verified in CFA-induced arthritis model by increasing hot plate test and von Frey test, and in mustard-oil-induced ear-inflammation via edema and via neutrophyl accumulation as well. Sitagliptin was more potent in the mustard-oil-induced ear-inflammation modell. 4. Both gliptins significantly inhibited capsaicin-induced plasmaextravasation in the urinary bladder in mice. In this measurement vildagliptin showed higher impact. 5. The different influence in various experiments suggests that they do not act in the same way. 6. Our results lead to the conclusion that both substances represent promising options for the therapy of inflammatory disorders. 7. The present study provides evidence that 30 min/day, whole body exposure to inhomogeneous SMF significantly diminishes plasma glucose level as compared to control in diabetic mice. Blood glucose level of mice not treated with STZ remained on the normal level with or without SMF exposure. 8. We did not experienced difference in body weight between SMF exposed and not exposed animals neither in healthy nor in diabetic status. 9. We did not experienced significant difference in peripheral nociception between exposed and sham animals neither in healthy nor in diabetic status.N

Comparative Investigation of Cellular Effects of Polyethylene Glycol (PEG) Derivatives

Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 4000, PEG 8000, PEG 10,000, 12,000, and PEG 20,000. The investigated cellular effects included cytotoxicity (MTT and Neutral Red assays, flow cytometry with propidium iodide and annexin V) and autophagy. The osmolality of different molecular weight PEGs with various concentrations was measured by a vapor pressure osmometer OSMOMAT 070 and G. mellonella larvae were injected with the solutions of PEGs. Sorbitol was used as controls of the same osmolality. Statistical correlation was calculated to describe the average molecular weight dependence of the different measured effects. Osmolality, the cytotoxicity assays, flow cytometry data, and larvae mortality had significant correlation with the structure of the PEGs, while autophagosome formation and the proportion of early apoptotic cells showed no statistical correlation. Overall, it must be noted that PEGs must be tested individually for biological effects as not all effects can be estimated by the average molecular weight

Matrix systems for oral drug delivery: formulations and drug release

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Matrix systems for oral drug delivery: Formulations and drug release

In this current article matrix formulations for oral drug delivery are reviewed. Conventional dosage forms and novel applications such as 3D printed matrices and aerogel matrices are discussed. Beside characterization, excipients and matrix forming agents are also enlisted and classified. The incorporated drug could exist in crystalline or in amorphous forms, which makes drug dissolution easily tunable. Main drug release mechanisms are detailed and reviewed to support rational design in pharmaceutical technology and manufacturing considering the fact that R&D members of the industry are forced to obtain knowledge about excipients and methods pros and cons. As innovative and promising research fields of drug delivery, 3D printed products and highly porous, low density aerogels with high specific surface area are spreading, currently limitlessly. These compositions can also be considered as matrix formulations

Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells

Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-β-cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization

Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells

Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-&beta;-cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization