A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Antibacterial activity of indium curcumin and indium diacetylcurcumin

Studies on curcumin, the principal element of turmeric powder, have demonstrated several biological actions such as antibacterial activity. Evaluation of new analogs or new compounds of curcumin for their antibacterial effect is interesting for researchers. In this in vitro study, we attempted to test the antibacterial activity of indium curcumin (In(CUR)3), indium diacetylcurcumin (In(DAC)3), and diacetylcurcumin (DAC) in comparison with curcumin. The action of these agents were examined on Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 14990), Pseudomonas aeruginosa (ATCC 27853), and Escerichia coli (ATCC 25922). Curcumin was effective against S. aureus and S. epidermidis, whereas In(DAC)3 showed activity against S. epidermidis and P. aeruginosa. The effect of In(DAC)3 on P. aeruginosa is an advantage. Strikingly, In(CUR)3 exhibited antibacterial activity on all the four mentioned strains. DAC did not show antibacterial effect on any of the four test bacteria. The minimum inhibitory concentration (MIC) of curcumin was 187.5 μg/ml for S. aureus, and 46.9 μg/ml for S. epidermidis. However, the MIC of In(CUR)3 was lower for the same bacterial strains (93.8 μg/ml for S.aureus and 23.4 μg/ml for S. epidermidis). Therefore, In(CUR)3 was found to have more antibacterial effect than curcumin itself and could be a suitable candidate for further in vivo investigations

Preparation and physicochemical characterization of prazosin conjugated PLGA nanoparticles for drug delivery of flutamide

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L‑lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1 H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficac

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Effect of Moisture Content on Terminal Velocity of Chickpea Varieties

Abstract Terminal velocity of four Iranian varieties of chickpea seeds at six moisture contents levels, experimentally and using mathematical model was obtained. The maximum and minimum values of experimental terminal velocity were obtained for jam and Kaka variety, respectively. The results showed that moisture content have significant effects on terminal velocity in each four varieties. As moisture content increased from around 7 to 25% (w.b.), terminal velocity of jam, ILC, Pirooz and Kaka seeds increased from 13.9 to 15.1, 12.79 to 13.67, 11.35 to 11.88 and 10.21 to 10.88 m/s, respectively. The results also show that suggested mathematical model can be used for prediction the terminal velocity of chickpea varieties, successfully. The coefficients of determination (R 2 ) in predicting terminal velocity for Kaka, Pirooz, ILC and jam varieties were 0.918, 0.903, 0.854 and 0.915, respectively

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD), particle size analyzer and differential scanning calorimetry (DSC). Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR) spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models

The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

<p>Abstract</p> <p>Background</p> <p>Experimental studies indicate that gamma linolenic acid (GLA) and docosahexaenoic acid (DHA) may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo.</p> <p>Methods</p> <p>GLA oil (GLAO; 72% GLA), DHA oil (DHAO; 73% DHA) were fed to adult wistar rats (1 mL/rat/day) starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid). Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7), epidermal growth factor receptor (EGFR), peroxisome proliferator activated receptor γ (PPAR-γ) and retinoid × receptor-α (RXR-α) were determined in a set of 18 animals per group.</p> <p>Results</p> <p>DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA) concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group.</p> <p>Conclusion</p> <p>Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.</p

Interrelationships and genetic analysis of seed yield and morphological traits in mini core collection of Iranian landrace, breeding lines and improved chickpea (Cicer arietinum L.) cultivars

To determine the association between genetic parameters and morphological traits in chickpea (Cicer arietinum L.) genotypes, a field experiment was conducted with 49 different landrace, breeding lines and cultivated chickpea genotypes using a 7×7 lattice square design with 2 replications in the 2012-2013 growing season. Genetic parameters including genetic, environmental and phenotypic variances; coefficients of variation; heritability; correlation coefficients; factor analysis and path coefficients were estimated, and cluster analysis was performed. High heritability values observed in measured traits indicating that these traits are controlled mainly by additive genes and that selection of such traits may be effective for improving seed yield. Number of seeds per plant, 100-seed weight and plant biomass had a positive direct effect on seed yield. These traits also had positive and highly significant phenotypic correlations with seed yield. Using principal component (PC) analysis, the first three PCs with eigenvalues more than 1 contributed 70.94% of the variability among accessions. The germplasm were grouped into 3 clusters. Each cluster had some specific characteristics of its own and the cluster I was clearly separated from cluster II and III. Overall the results, it can be concluded that seed yield in chickpea can be improved by selecting an ideotype having greater number of seeds per plant, 100-seed weight and plant biomass

A laboratory and glasshouse evaluation of ascorbic and salicylic acid effect on germination traits and grain yield of safflower cultivars

Abstract Information regarding the evaluation of ascorbic and salicylic acid on safflower cultivars germination traits is not available. The study, consisting of two experiments (laboratory and glasshouse), was conducted as a factorial experiment with randomized design and three replications. Factor A included six priming treatments (50 mg , 100 mg L -1 ASA, hydro-priming and control) and factor B included three safflower cultivars (&apos;Faraman&apos; , &apos;Sina&apos; and &apos;IL 111&apos;). Results showed that the highest shoot length (4.71 cm) was observed in the 50 mg L -1 SA treatment and the lowest length was 1.24 cm, in the control treatment. The longest (3.71 cm) and shortest (1.06 cm) radicles were observed in hydroprimed &apos;Faraman&apos; and &apos;IL111&apos; ASA100 treatments, respectively. Also, the highest (8.32 mg) and lowest (1.96 mg) radicle weights were observed in &apos;Faraman&apos; SA50 and &apos;IL111&apos; AsA100 treatments, respectively. For all cultivars, as SA and ASA concentration increased, the emergence rate index decreased. The highest grain yield (16.2 g per plant) was observed for the &apos;Faraman&apos; cultivar

Responses of soil microbial biomass and enzyme activities to tillage and fertilization systems in soybean (Glycine max L.) production

Tillage operation and fertilizer type play important roles in soil properties as far as soil microbial condition is concerned. Information regarding the simultaneous evaluation of the effect of long-term tillage and fertilization on the soil microbial traits of soybean farms is not available. Accordingly, it was hypothesized that, the microbial biomass and enzyme activity, more often than not, respond quickly to changes in soil tillage and fertilization. Therefore, the experiments were aimed at analyzing the responses of soil microbial traits to tillage and fertilization in a soybean field in Kurdistan University, Iran. The field soil is categorized into coarse Loamy, mixed, superactive, calcareous, and mesic Typic Xerorthents. The experiments were arranged in split plot, based on randomized complete block design with three replications. Main plots consisted of long-term (since 2002) tillage systems including conventional tillage (CT), minimum tillage (MT) and no-tillage (NT). Eight fertilization methods were employed in the sub-plots, including (F1): farmyard manure (FYM); (F2): compost; (F3): chemical fertilizers; (F4): FYM + compost; (F5): FYM + chemical fertilizers; (F6): compost + chemical fertilizers; (F7): FYM + compost + chemical fertilizers and (F8): Control (without fertilizer). The highest microbial biomass carbon (385.1 μg) was observed in NT-F4 treatment. The NT treatment comparatively recorded higher values of acid phosphatase (189.1 μg PNP g-1 h-1), alkaline phosphatase (2879.6 μg PNP g-1 h-1) and dehydrogenase activity (68.1 μg PNP g-1 h-1). The soil treated with a mixture of compost and FYM inputs had the maximum urease activity of all tillage treatments. Organically manured treatment (F4) showed more activity in dehydrogenase (85.7 μg PNP g-1 h-1), acid phosphatase (199.1 µg PNP g-1 h-1) and alkaline phosphatase (3183.6 µg PNP g-1 h-1) compared to those treated with chemical fertilizers. In NT-F4 treatment, using on-farm inputs is most suitable for sustainable management and improvement in soil biological activities in soybean cultivation. We concluded that applying organic manures and employing reduced tillage systems increased soil microbial biomass and enzyme activities