Volume 64 (2014): Issue 2 (June 2014)

The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive gel base for econazole nitrate and miconazole nitrate. To this aim, different types of chitosan with different molecular masses and viscosity properties [low molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa s)] have been used. First, rheological studies were conducted on chitosan gels. Mechanical, syringeability and mucoadhesive properties of chitosan gels were determined. Release profiles of econazole nitrate and miconazole nitrate from chitosan gels were obtained and evaluated kinetically. In addition, anticandidal activities of formulations were determined. Finally, vaginal retention of chitosan gels in rats was evaluated by in vivo distribution studies. Based on the results, it can be concluded that gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retention

It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase- 1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine- -proline-cysteine (CRMYPC) and cysteine-arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC) have good residual interactions with the target and the binding energy ΔG_binding of -31.7402 and -31.0144 kcal mol-1, respectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1

The objective of this study was to screen extracts of twenty Eastern European medicinal plants, using wild-type and reporter Chromobacterium violaceum bioassays, for novel components that target bacterial cells and their quorum sensing (QS) communication systems. Three types of activity and their combinations were revealed: (i) direct antimicrobial growth-inhibitory activity, (ii) non-specific and specific pro-QS activities, (iii) anti-QS activity. Among seven plant extracts showing direct growth-inhibitory activity, the strongest effect was shown by Arctostaphylos uva- -ursi (bearberry) leaves. Many plants stimulated violacein production by wild-type C. violaceum ATCC 31532 in a non-specific manner, and only the herb Bidens tripartita (three-lobe beggarticks) contained compounds that mimic acyl-homoserine lactone and operated as a QS agonist. Anti-QS activity was found in eleven plants including Quercus robur (oak) cortex, Betula verrucosa (birch) buds and Eucalyptus viminalis (Manna Gum) leaves. Subsequent statistical analysis showed differences between antimicrobial and anti-QS activities, whereas both activities were defined by phylogenetic position of medical resource plant. Finally, extract from Quercus robur cortex revealed at least two fractions, showing different anti-QS mechanisms. These data confirm that multicomponent anti-infectious mechanisms are used by plants, which may be useful for drug development

A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith® Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min^-1. The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ≥ 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL^-1. The limits of detection were 2.34 and 0.03 ng mL^-1 for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run- -time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT

Catechins may influence both desirable and undesirable effects of many drugs. In this study, the in vitro effect of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate (EGCG) on the efficacy of anticancer drug doxorubicin (DOX) was studied in HCT-8 cancer cells. Rat hepatocytes were used to study the influence of EGCG on DOX hepatotoxicity. Cell proliferation and viability were studied by 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and neutral red uptake test assays. Formation of reactive oxygen species (ROS) was determined using the dichlorofluorescein assay. All of the studied catechins (1-25 μmol L^-1) had no effect on the proliferation of intestinal cancer cells and did not affect the antiproliferative effect of DOX (1-8 μmol L^-1) in these cells. Moreover, EGCG at 25 μmol L^-1 increased the viability of isolated hepatocytes and significantly protected these cells against DOX-induced toxicity and ROS production. Consumption of EGCG during DOX therapy seems to be safe and beneficial, since EGCG does not decrease DOX anticancer efficacy and could ameliorate DOX hepatotoxicity

To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG

There are a number of compounds that can modify the activity of ABC (ATP-binding cassette) and SLC (solute carrier) transporters in the blood-brain barrier (BBB). The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A, quercetin) substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4-thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the title compounds was elucidated by elemental analysis, IR, 1H and 13C NMR spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated for their ex vivo spasmolytic potential on four isolated smooth muscles (rat aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine. Some of the compounds exhibited potent spasmolytic activity equal to or stronger than scopolamine

In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

The aim of the study was to examine the effect of topical vehicles on the in vivo human stratum corneum penetration of the antioxidant and skin photoprotective agent (-)-epigallocatechin-3-gallate (EGCG). Model oil-in-water (o/w) emulsion and gel formulations containing 1 % (m/m) EGCG were prepared and subjected to photodegradation studies in order to select excipients that minimize the light instability of EGCG. The optimized emulsion and gel were applied to human volunteers and the EGCG percutaneous permeation was evaluated in vivo by the tape- -stripping technique. No significant differences in the percentage of the applied EGCG dose diffused into the stratum corneum were observed between the o/w emulsion (36.1 ± 7.5 %) and gel (35.5 ± 8.1 %) preparations. However, the amount of EGCG permeated into the deeper region of human stratum corneum was significantly larger for the o/w emulsion compared to the gel. Therefore, the emulsion represents a suitable vehicle for topical delivery of EGCG.