Core shell methyl methacrylate chitosan nanoparticles: in vitro mucoadhesion and complement activation

Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione [GSH] to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum [HS] by measurement of the hemolytic capacity of the complement system after contact with nanoparticles. The FT-IR and 1HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate [MMA] homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan

[Evaluation of anti-Helicobacter pylori activity of methanol extracts of some species of Stachys and Melia]

The gram-negative bacterium Helicobacter pylori [H. pylori], identified in 1982, is now recognized as the primary etiological factor associated with the development of gastritis and peptic ulcer disease. The growing problem of antibiotic resistance by the organism demands the search for novel compounds from plant based sources. The present study is aimed at evaluating the anti-Helicobacter pylori activity of 10 Iranian plant extracts on clinical isolates of H. pylori. Gastric biopsy samples were obtained from patients presenting with gastroduodenal complications. H. pylori was isolated from the specimens following standard microbiology procedures. The disk diffusion method was used to determine the susceptibility of 12 isolates to methanol plant extracts [Fruit and leaves of Melia azedarach, Melia indica and aerial parts of Stachys setifera, Stachys turcomanica, Stachys trinervis, Stachys subaphylla, Stachys byzanthina, Stachys persica, Stachys inflata, Stachys laxa]. The plants tested at 8 mg/disc concentration demonstrated anti-Helicobacter pylori activity with zone diameters of inhibition ranging from 12-38 mm. Of these, Stachys setifera [aerial parts], Melia indica [Fruit] and Melia azedarach [leaves] showed the most potent anti -H. pylori activity on the isolates. Due to the rise in antibiotic resistance, new sources of anti-H. pylori drugs are needed. The use of medicinal plants may have potential benefit in eradicating such problems. According to the results of this study, further studies will be necessary to investigate the effects of other plants of Iran against H. pylori infectio

[Polyclonal antibody production against bovine serum albumin conjugated artemisinin in rabbit]

The aim of the present study was to produce a polyclonal antibody against bovine serum albumin [BSA] conjugated with artemisinin. To gain an immunogenic character of artemisinin, a carboxyl group was added to it using mixed anhydride method. Then, the reactive compound of artemisinin was conjugated with BSA. The BSA+artemisinin were injected to white female New Zealand rabbits for two times. In the first injection, the Fraud's complete adjuvant was used, and two weeks later, a booster injection was carried out with a Fraud's incomplete adjuvant. Two weeks later, blood samples were collected; their serum were separated and frozen until assessment. The production of antibody against BSA+artemisinin was assayed by Immunoblot technique. Antibody was separated and concentrated by saturated ammonium sulfate. The assay confirmed the successful production of an antibody against BSA+artemisinin as a fundamental step in investigation of pharmacodynamics and pharmacokinetics of artemisinin

In vitro evaluation the effect of 1, 3, 4, thiadiazole new derivatives against

The main therapeutic compounds available against Leishmaniasis disease is pentavalent antimonyfcg compounds i.e. Glucantime and Pentostam. New antileishmanial compound is needed due to the emerge of drug-resistant leishmania agents in recent years. In the present study the antileishmanial activity of new 1, 3, 4 thiadiazole derivatives were evaluated. Promastigote stages of the parasites were cultured in RPM1-1640 containing 10% FBS, 100 lU/ml penicillin and 100 micro g/ml streptomycin. Mouse peritoneal exudate macrophages [MPEM] isolated from the peritoneal cavity of BALB/c mice were used and the macrophages were counted and the cell suspension was adjusted to 5X10[5] cell/ml. Macrophage monolayers in 8-well chamber slides were infected with stationary phase promastigote, at a 5:1 parasite/cell proportion and incubated at 37°C and 5% CO[2]. Serial dilution of thiadiazole compounds and tartar emetic as the control was added to the slide chambers and parasite survival index [PSI] was measured after 5 days. The Thiazolyl blue reduction [MTT test] was used to determine the antileishmanial effect of the compounds on extra celluto forms of the parasite and after 72 h. The CD's were read by 96-well scanner and IC[50] were calculated. Two thiadiazole compounds showed 6-67% antileishmanial activity in 4.6 micro g/ml concentration against intracellular forms of the parasites and also in MTT assay IC[50] of 3.6 -7.6 micro g/ml was determined. Due to high antileishmanial activity of some compounds, further studies on structure and activity of these compounds and new highly active derivatives is expected

Synthesis and anticonvulsant activity of novel 2-amino-5-[4-chloro-2-[2-chlorophenoxy] phenyl] -1, 3, 4-thiadiazole derivatives

Several novel 2-amino-5-[4-chloro-2-[2-chlorophenoxy]phenyl]-1, 3, 4-thiadiazole derivatives 4a-d were synthesized and their anticonvulsant activity was determined by evaluation of the ability of theses compounds to protect mice against convulsion induced by a lethal doses of pentylentetrazole [PTZ] and maximal electroshock [MES]. The result of anticonvulsant data shows that among the synthesized compounds, 5-[4-chloro-2-[2-chlorophenoxy]phenyl]-N-ethyl-1, 3, 4-thiadiazol-2-amine 4c was the most active compound in both MES and PTZ tests with an ED[50] of 20.11 and 35.33 mg/kg, respectively