Functionalized mesoporous silica nanoparticles for oral delivery of budesonide

Non-functionalized and amino-functionalized mesoporous silica nanoparticle were loaded with anti-inflammatory drug budesonide and additionally post-coated with bioadhesive polymer (carbopol). TEM images showed spherical shape of the nanoparticles and slightly higher polydispersity after coating with carbopol. Nitrogen physisorption and thermogravimetic analysis revealed that more efficient loading and incorporation into the pores of nanoparticles was achieved with the amino-functionalized silica carrier. Infrared spectra indicated that the post-coating of these nanoparticles with carbopol led to the formation of bond between amino groups of the functionalized carrier and carboxyl groups of carbopol. The combination of amino-functionalization of the carrier with the post-coating of the nanoparticles sustained budesonide release. Further, an in vitro model of inflammatory bowel disease showed that the cytoprotective effect of budesonide loaded in the post-coated silica nanoparticles on damaged HT-29 cells was more pronounced compared to the cytoprotection obtained with pure budesonide

Effect of cytisine on some brain and hepatic biochemical parameters in spontaneously hypertensive rats

Tobacco smoking is a risk factor for variety of cardio-vascular diseases, such as hypertension, myocardial infarction, stroke and many others. It is of great importance for hypertensive patients to stop smoking. One of the medicines widely used for smoking cessation in Bulgaria is the original Bulgarian product Tabex®, which is developed on the basis of natural plant alkaloid cytisine. The aim of the following study was to ivestigate the effects of cytisine on some brain and hepatic biochemical parameters in spontaneously hypertensive rats (SHR), an widely used rodent model for human essential hypertension, and to compare the obtained results with their age-matched normotensive controls Wistar Kyoto (WKY). Multiple cytisine administration did not affect the activity of ethylmorphine-N-demethylase (EMND) and anylinehydroxylase (AH), as well as the quantity of cytochrome P 450, nor in WKY neither in SHR In the liver cytisine increased the MDA quantity both in SHR and in WKY, by 25% (p<0.05) and by 29% (p<0.05) respectively, while the GSH level was not significantly changed by the compound in both strains. In contrast, on the brain level, cytisine administration to SHR caused more prominent toxicity, resulted in GSH depletion and increased MDA quantity, while in WKY strain did not exert any toxicity. Cytisine did not significantly affect ALAT and ASAT activity in both strains. In conclusion, the results of our study suggest higher brain toxicity of cytisine in spontaneously hypertensive rats, that might be due to their pathophysiological characteristics

Drug-drug interactions and adverse drug reactions with classicand new anticoagulants

Drug interactions and adverse drug effects (ADR) have received much attention because many patients are being hospitalized or remaining hospitalized longer than necessary. Use of multiple drugs (8-12 on average in hospitalized patients) is common in a number of therapeutic regimens. Anticoagulant drugs are among the most commonly implicated medications that cause ADR in hospitalized patients and medication errors involving anticoagulant drugs remain common. Elderly and cardiac patients represent populations at particularly high risk for suffering anticoagulant - associated ARD and drug interactions. In this study we review clinically significant pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) involving classic and new anticoagulants. A literature search was conducted via PubMed and the Cochrane database to identify drug-drug interaction studies, using the terms drug interactions, adverse drug reactions oral anticoagulants, including dabigatran, rivaroxaban, and apixaban. Articles reviewed focused on drugs affecting the permeability glycoprotein (P-gp) efflux transporter protein and/or cytochrome P (CYP) 450 3A4 enzymes, and pharmacodynamic DDIs when drugs are administered concomitantly.Awareness of drugs that are involved in drug-drug interactions and especially those that alter the function of the P-gp efflux transporter protein and CYP3A4 enzymes and provide adverse effects should enable medical doctors to anticipate and avoid potential DDIs involving the anticoagulants.Key words: antocoagulant therapy, drug interactions, adverse drug reaction

PRECISION-CUT SLICES AS A TOOL FOR STUDYING PHASE II DRUG METABOLISM IN RAT SMALL INTESTINE IN VITRO

A wide range of endogenous and exogenous compounds including many drugs and their metabolites are inactivated by phase II drug metabolism enzymes UDP-glucuronyltransferase and glutathione S-transferase. The aim of the study was to set up an intestinal precision-cut slice technique for evaluating phase II drug metabolism in rat small intestine. The enzyme activity of UDPglucuronyltransferase and glutathione S-transferase was measured up to 4 h of incubation and compared with those from intestinal cells obtained by mucosa scraping technique. The results from our study suggest that the activity of both phase II drug metabolism enzymes remains constant at least for a period of 4 h. Both intestinal preparations exhibit phase II metabolic activities at similar rates, but precision-cut intestinal slices have a longer life span. They remain viable up to 24 h of incubation. Precision cut slices might be reliable and quite simple system for evaluating xenobiotic phase II metabolism in rat intestine in vitr