Journal of Reports in Pharmaceutical Sciences
Volume:2 Issue: 1, Jan-Jun 2013

The hydro-distilled volatile oils, obtained from dried endocarp and hulls of Persian bay laurel (Laurus nobilis var. angustifolia) from Laueaceae family were analyzed by GC/MS. Thirteen and twelve compounds consisting 81.6% and 89.1% of the total components were identified of the oils obtained with a yield of 3% and 1.2% (w/w) respectively. Differences of some compounds between endocarp and hulls oils were evinced. While the oil of endocarp contained 1,8-cineole (46.7%), α-terpinyl acetate (7.4%), β-pinene (7.3%) and α-phellandrene (4.7%), the oil of hulls contained 1,8-cineole (40.5%), trans-β-ocimene (22.1%), caryophyllene oxide (6.9%) and α-terpinyl acetate (5.0%).

A series of 3-hydroxypyridin-4-one derivatives (HPOs) as bidentate iron (III) chelating agents were synthesized from 3-hydroxypyran-4-ones (maltol and ethyl maltol) in three steps through protection of hydroxyl group. The protected compounds were then reacted with suitable primary amines to give benzylated pyridinones. Finally, the benzyl group was removed by catalytic hydrogenation to produce the desired products. The partition coefficient of the free ligands and their iron (III) complexes were determined in an aqueous/octanol system using shake-flask method. The cytotoxic effects of these iron chelators against MCF-7 and MDA-MB-231 cancer cells were also evaluated using MTT assay. The results revealed that cytotoxicity of synthesized compounds were closely related to the lipophilycity of them so that the most lipophilic compound (4f) showed the highest activity; whereas compound 4a as a more hydrophilic agent showed the lowest cytotoxic effect; Although these compounds were cytotoxic at high concentration (≥ 0.1 mM)

Adenosine deaminase (EC, 3.5.4.4), is a metalloenzyme contain a zinc ion. This enzyme plays a key role in purine metabolism and irreversible hydrolysis of adenosine and 2´-deoxy adenosine to inosine, 2´-deoxy inosine and ammonia. Adenosine deaminase inadequacy leads to severe combined immunodeficiency disease. Understanding the interaction of adenosine deaminase with inhibitors is crucial for the development of pharmaceutical agents. Computer simulations show these interactions. In the present study, was considered the interactions between 6 inhibitors and adenosine deaminase by binding free energy calculation. We used docking and molecular dynamic simulation method to determine inhibitors binding free energy. In all, was performed the 60 ns molecular dynamic simulations for free inhibitors and 60 ns molecular dynamics simulations for inhibitor-enzyme complex. At the end, the inhibitors free energy of binding was calculated by using the linear interaction energy method. Our results clearly showed that non polar interactions play a significant role in determining the binding free energy. The results also demonstrated that the inhibitor binding site is a hydrophobic pocket that completely is surrounded by the hydrophobic residue. We also found that the stronger binding lead to further reduction of solvent accessible surface area the inhibitor in the inhibitor-enzyme complex. Also, it was found that the inhibitor 6 (butyl 3-(6-amino-9H-purine-9-yl) propanoate have the lowest binding free energy and the maximum number of hydrogen bond between the inhibitor and adenosine deaminase so that it makes a greater interactions and can be used for a more considerations and empirical studies.

A new type of drug delivery system known as mucoadhesive film has been developed for oral thrush treatment. Due to comfortable use of this drug delivery system, this would be encouragingly utilized, especially in babies and patient under chemotherapy. Nystatin mucoadhesive film (NMF) is a polymeric film which is adhered to front upper gum and back to the upper lip and releases the drug within 5-6 hours in desired concentration. Because of sustained-release nature and permanent contact of drug with infectious agent of Candida albicans, the disease amelioration would be happened more rapidly while the patients can do routine activities such as eating, drinking and talking without any feeling of the existence of film in their mouth cavity. NMF film was prepared using Eudragit RL100 and HPMC as film-forming constituents, and glycerin, propylene glycol and poly ethylene glycol 400 as plasticizer, according casting method. Finally, physical appearance, weight, in vitro drug release rate and adhesion were assessed. In respect to considered parameters, prepared films with HPMC were not shown uniform appearance; however, prepared films with Eudragit RL100 were shown more desirable results and later shown longer time of drug release with approximate time of 5.5 hours. Prepared films with dimensions of 2×1 cm containing 10 mg nystatin using Eudragit RL100 polymer with mixture of glycerin, propylene glycol as plasticizer, not only shown desirable pharmaceutics characteristics but also exponential value (n) of 0.779 showed non-Fickian behavior of drug release.

Sustained release oral delivery systems are designed to achieve therapeutically effective concentrations of drug in the systemic circulation over an extended period of time. The purpose of the present investigation was to design and evaluate sustained release matrix tablets of nifedipine, a poorly water soluble drug, employing hydroxypropyl methyl cellulose (HPMC) and ethyl cellulose (EC) as hydrophilic polymers. Direct compression method was used to prepare matrix tablets. Drug content uniformity, friability test were performed and the in vitro drug release profiles were compared with the innovator product (Procardia) benefiting similarity factor (f2) and difference factor (f1). In all formulations content uniformity was in the acceptable range. Most of the prepared formulations were passed friability test. Formulation containing HPMC and EC in the ratio of 88.5:5 showed acceptable dissolution properties compared to reference formulation. Fitting the release data to the kinetic models indicated that the best fitted kinetic model for the prepared matrix tablets and Procardia were zero order and Weibull model, respectively. This study indicates that the hydrophilic matrix tablets of nifedipine prepared using HPMC and EC can successfully be employed as sustained release matrix tablet in order to improve patient compliance.

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, has been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activity of two synthesized COX-2 inhibitor derivatives (A and B) on human myeloid leukemia (K562) and breast adenocarcinoma (MCF-7) cancer cells has not been well established. This study was designed to investigate the morphological changes of compounds A and B –treated cells as well as DNA cleavage activity of these compounds. The DNA cleavage experiments were performed by agarose gel electrophoresis. Plasmid pTZ57 DNA was treated with the compounds A and B at various concentrations. Then, bands visualized by UV light and photographed to determine the extent of cleavage of the supercoiled (SC) to Nicked (NC) DNA. Furthermore, the apoptotic activities of the two compounds were assessed using cells treated DAPI staining method. The results obtained from DNA cleavage assay demonstrated that with the increasing concentration of compound A, SC DNA is gradually converted to NC DNA. Cells were also exposed to various concentrations (0.1-100 μM) of each compound for 24 h. All compounds demonstrated remarkable cytotoxic effect on MCF-7 and K562 cell lines in a concentration-dependent manner with IC50 values ranging between 6.5–22.23 μM. Treatment of the cells with compounds A and B significantly cause morphological changes after 16 h. Collectively, our data indicate that compounds A and B as two COX-2 derivatives may present promising chemotherapeutic agents, possibly targeting DNA and inducing cell death in the selected cancer cell line which needs further research.

Chlorpheniramine maleate is a widely used antihistaminic drug but it is very bitter and as yet no mouth dissolving/disintegrating taste-masked preparation that might be useful in pediatric and geriatric patients is available in the market. The aim of this study was to prepare a microsphere formulation in order to mask the bitter taste of chlorpheniramine. Microspheres of chlorpheniramine with pH-dependent polymers (such as Eudragits S100, L100 and L100-55) were prepared by the double emulsion solvent diffusion method. The effect of different polymers and drug–polymer ratios on the taste masking and the characteristics of the microspheres were investigated. At first, the drug dissolved in water and polymer dissolved in an organic solvent that was composed of ethanol (good solvent) and dichloromethane (bridging liquid) with 2:1 ratio. Silica is a good anti-adhesion agent against the viscous characteristic of polymers and disperses into dichloromethane. In the current study formulations with different drug/polymer ratio were prepared and were characterized by drug loading, loading efficiency, yield, particle size, x-ray diffraction (XRD), fourier transform spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vitro release studies were performed in pH 1. 2 and 7. 4. The best polymer to drug ratio in microparticles Eudragit L100 and L100-55 were F''3 and F«3 (7:1) which showed 9. 67% and 7. 88% of entrapment, loading efficiency 77. 34% and 63. 08% and mean particle size of 12. 484 µm and 10. 675 µm, respectively. The drug loading microparticle Eudragit S100 (5:1) showed 9. 65% of entrapment, loading efficiency 57. 92% and mean particle size of 6. 807 µm. The FTIR, XRD and DSC showed the stable character of clorpheniramine in the drug-loaded microspheres and revealed an amorphous form. The results showed that microparticles prepared with pH-dependent polymers were slower release than the commercial tablet (p< 0. 05). The results demonstrated that Eudragit S100 was the best for masking the unpleasant taste of chlorpheniramine among the three polymers investigated. The results indicated that the microsphere formulation could be a promising drug carrier for masking the bitter taste of chlorpheniramine.

The purpose of this study was to develop sunless tanning cosmetic creams from green coffee beans. Chlorogenic acid, which was extracted from green coffee beans, performed the change of the color of keratin in stratum corneum, used as active ingredient in the formulation. Extracted chlorogenic acid from green coffee beans were incorporated into four cosmetic cream bases, and then the tanning effect of the creams were evaluated as well as the stability test of the creams. The results showed that O/W cream base with extracted chlorgenic acid from green coffee beans had the most tanning activity at pH 4.5±0.5 and 40oC. The O/W cream also performed most stable than the other two types of cream. In conclusion, sunless tanning product from green coffee beans might be formulated in O/W type cream.

Curcumin is a natural polyphenolic compound with anti-cancer, anti-inflammatory, and anti-oxidation properties. Low water solubility and rapid hydrolytic degradation are two challenges limiting use of curcumin as therapeutic agent. In the current study, the role of the native/modified forms of bovine serum albumin (BSA) and casein, as food-grade biopolymers and safe drug delivery systems, on the physical and biological activity of curcumin were surveyed. Analyses of quenching of proteins fluorescence by curcumin indicated that chemical modification decreased binding affinity of curcumin toward albumin whereas it significantly increased for casein and average number of binding sites also doubled in modified casein. Measurement of cell viability using LDH assay showed that cytotoxicity of protein-bound curcumin is higher than free curcumin. Moreover, in the presence of native proteins, curcumin revealed elevated in vitro anti-cancer activity (against MCF7 and SKNMC) compared to modified forms. It appears that BSA and casein as protein vehicles are useful tools to increase both food quality and the bioavailability of curcumin as health promoting agent. However, results imply that the chemical modification of proteins cannot improve the anti-cancer activity of curcumin despite increasing of their binding affinity.

A series of fluoroquinolone derivatives holding triazolidindione moieties have been synthesized and proved to be cytotoxic agents in vitro particularly against cancer cell lines (SKNMC, MCF7, A2780-CP, SW48, A549, KB, HT-29, HepG2). The cytotoxic activity was assessed using MTT colorimetric assay. Our compounds had less cytotoxicity than doxorubicin in all studied cell lines.

Fungal biomass of A. Niger, the byproduct of citric acid fermentation, proved to be a worth biomaterial which can be so beneficial and practical. In environmental case, it can be a useful biosorbent for decolorization and detoxitation of wastewater samples. It can also be used as a cheap and suitable source for commercial production of some expensive and useful biopolymers such as chitin, chitosan and food supplements such as chitin-glucan and glucosamine.