Preparation and Optimization of Controlled Release Nanoparticles Containing Cefixime Using Central Composite Design: An Attempt to Enrich Its Antimicrobial Activity.

BACKGROUND: Due to the increased resistance against existing antibiotics, research is essential to discover new and alternative ways to control infections induced by resistant pathogens. OBJECTIVE: The goal of the current scrutinization was to enrich the dissolution rate and antibacterial property of cefixime (CEF) orally. METHODS: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricated using the ionic gelation method. Central Composite design has been applied to get the optimal formulation for the delivery of CEF. The effect of three variables, such as the concentration of chitosan, tripolyphosphate, and tween 80, on the characteristics of NPs was evaluated. RESULTS: The optimized NPs involved a relatively monodispersed size distribution with an average diameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmed the size of NPs. The surface morphology of NPs was observed by scanning electron microscopy. The calorimetric analysis indicated the amorphous state of cefixime in the formulation. The dissolution rate of NPs in aqueous media was acceptable and the model of release kinetics for CEF from NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteria was hopefully efficient. The ex-vivo release study demonstrated higher penetration of NPs from the rat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation. CONCLUSION: Chitosan NPs could be considered a significant system for the controlled delivery of CEF due to its antibacterial effectiveness.

The Use of Two Bifidobacterium Strains Enhanced Growth Performance and Nutrient Utilization of Rainbow Trout (Oncorhynchus mykiss) Fry.

This study aims to evaluate the effects of Bifidobacterium animalis PTCC-1631 and Bifidobacterium lactis PTCC-1736 on growth, nutrient digestibility, carcass composition, and intestinal microbiota of Oncorhynchus mykiss fry, which had initial body weights of 0.58 ± 0.19 g. Four iso-nitrogenous diets with probiotics, namely T1 (1 × 107 CFU g-1), T2 (2 × 107 CFU g-1), T3 (3 × 107 CFU g-1), and control without probiotics were obtained. Total 480 fish were randomly divided in four treatments (three experimental treatments and a control), each with 4 replicates including 16 tanks each filled with 15 L-1 of water (water exchange rate of 2 L min-1 and aerated with air stone) with a density of 2 fry L-1. The water mean temperature was 17.66 ± 1.33 °C, and the mean pH value was 7.63 ± 0.08. After eight weeks of the experiment T1 that fed with a diet contained the lowest bacterial concentration showed higher growth, nutrient utilization, digestibility, and lower feed conversion ratio (P < 0.05) in comparison with T2, T3, and the control. Also, the highest count of lactobacillus bacteria was observed in T1 that was fed with a diet containing the lowest probiotic. The lowest concentration of Bifidobacterium strains in this study induced better growth and increased digestion and nutrient utilization in trout fry.

Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol.

Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not. Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm. Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value<0.001). Conclusion: This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol.

Isolation and characterization of homoisoflavonoids from Scilla persica HAUSSKN

abstract Medicinal plants have many traditional claims including the treatment of ailments of infectious origin. In the evaluation of traditional claims, scientific research is extremely important. In this study, five homoisoflavonoids named 3-(4'-hydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one(Autumnalin),3-(4'-hydroxybenzyl)-5,7-dihydroxy-6-methoxychroman-4-one (3,9-dihydro-autumnalin), 3-(3',4'-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one,3-(3',4'-dihydroxybenzylidene)-5,8-dihydroxy-7-methoxychroman-4-one and 3-(3',4'-dihydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one, were isolated from the bulbs of the plant Scilla persica HAUSSKN. Their structures were established on the basis of extensive spectroscopic analyses such as NMR, MS, IR and UV.

resumo Plantas medicinais apresentam muitas atribuições tradicionais, incluindo o tratamento de doenças de origem infecciosa. A pesquisa científica é extremamente importante na avaliação dos usos tradicionais. Neste estudo, cinco homoisoflavonóides: 3-(4'-hidroxibenzilideno)-5,7-diidroxi-6-metoxicroman-4-ona(autumnalina), 3-(4'-hidroxibenzil)-5,7-diidroxi-6- metoxicroman-4-ona (3,9-diidro-autumnalina), 3-(3',4'-diidroxibenzil)-5,8-diidroxi-7- metoxicroman-4-ona, 3-(3',4'-diidroxibenzilideno)-5,8-diidroxi-7- metoxicroman-4-ona e 3-(3',4'-diidroxibenzilideno)-5,7-diidroxi-6- metoxicroman-4-ona foram isolados dos bulbos da planta Scilla persica HAUSSKN. Suas estruturas foram estabelecidas com base na extensa análise espectroscópica, como RMN, EM, IV e UV.

Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design.

OBJECTIVES: A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. MATERIALS AND METHODS: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. RESULTS: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. CONCLUSION: This study showed that by controllinig the physical variables optimum drug release were obtained.

Microbial mediated preparation, characterization and optimization of gold nanoparticles

The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 ºC and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl4 solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl4, pH of medium and temperature of shaker incubator. The R² value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

Biochemical and biophysical properties of a novel homoisoflavonoid extracted from Scilla persica HAUSSKN.

In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3',4'-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a=11.7676 (2)Å, b=20.1174 (4)Å, c=7.8645 (9)Å, ß=93.544 (2)°, V=1858.23 (7)Å(3), monoclinic space group P21/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines.

Optimization of particle size and encapsulation efficiency of vancomycin nanoparticles by response surface methodology.

CONTEXT: Treating vancomycin-resistant Staphylococcus aureus strains requires high doses of vancomycin, which might lead to adverse reactions such as nephrotoxicity and "red neck syndrome". Use of nanotechnology for antibiotic delivery is a promising approach to overcome antibiotic-resistance. OBJECTIVE: The objective of this study was optimizing the particle size and encapsulation efficiency (EE) of vancomycin nanoparticles prepared from chitosan. MATERIALS AND METHODS: The nanoparticles were prepared by ionotropic gelation method, at different combinations of chitosan concentration, chitosan/tripolyphosphate mass and vancomycin/chitosan mass, using Box-Behnken experimental design. Dynamic light scattering and ultracentrifugation were used to measure the nanoparticle size and EE, respectively. Vancomycin was quantified in samples by spectrophotometery. The optimum conditions were determined by subsequent regression analysis and multicriteria decision analysis of the output data. RESULTS: The nanoparticle size and EE were greatly influenced by the independent variables, which had interactive effects on both responses. The optimum conditions for production of nanoparticles were chitosan concentration of 0.5-1.2 mg/ml, chitosan/tripolyphosphate mass ratio of 3-3.5 and vancomycin/chitosan mass ratio of 1, which yielded nanoparticles between 130 and 150 nm with encapsulation efficiencies of 60-69%. CONCLUSIONS: The size and EE of vancomycin nanoparticles were optimized by the proposed procedure.

Microbial mediated preparation, characterization and optimization of gold nanoparticles.

The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 °C and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl4 solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl4, pH of medium and temperature of shaker incubator. The R(2) value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

Optimization of size and encapsulation efficiency of 5-FU loaded chitosan nanoparticles by response surface methodology.

The objective of this study was to optimize the particle size and encapsulation efficiency of chitosan nanoparticles loaded with 5-Fluorouracil (5-FU) by response surface methodology. Nanoparticles were prepared by ionic gelation method from chitosan and penta sodium triphosphate (TPP) at different combinations of chitosan viscosity, chitosan concentration and chitosan/TPP mass ratio according to the Box-Behnken experimental design. The particle size and encapsulation efficiency of prepared particles were measured by dynamic light scattering and UV spectroscopy, respectively, and the obtained data were subjected to multiple linear regression analysis followed by multi-attribute utility analysis to obtain a model for prediction of the optimum response. The optimum conditions for the production of 5-FU loaded chitosan nanoparticles were found to be low viscosity chitosan 0.5-1 mg/mL, middle viscosity chitosan 0.5-0.8 mg/mL and high viscosity chitosan 0.5-0.75 mg/mL and chitosan/TPP mass ratio of 4 or 6, yielding nanoparticles at the average diameter range of 114-188 nm and encapsulation efficiencies between 42-55%.

Efficient synthesis of stable phosphonate ylides and phosphonate esters: reaction between activated acetylenes and triphenylphosphite in the presence of sulfonamide and heterocyclic NH-acids.

An efficient synthesis of stable phosphonate ylides and phosphonate esters is described via a one-pot reaction between activated acetylenes and triphenylphosphite in the presence of sulfonamides and heterocyclic NH-acids. Single X-ray diffraction analysis and NMR studies were used in characterizing the ylides and phosphonate ester products. Dynamic NMR studies performed on a phosphonate ylide allowed the calculation of the free energy barrier for the inter-conversion between the geometrical isomers (E) and (Z).