Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique

Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 μm, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.     

A novel connectionist framework for computation of an approximate convex-hull of a set of planar points, circles and ellipses

We propose a two layer neural network for computation of an approximate convex-hull of a set of points or a set of circles/ellipses of different sizes. The algorithm is based on a very elegant concept - shrinking of a rubber band surrounding the set of planar objects. Logically, a set of neurons is placed on a circle (rubber band) surrounding the objects. Each neuron has a parameter vector associated with it. This may be viewed as the current position of the neuron. The given set of points/objects exerts a force of attraction on every neuron, which determines how its current position will be updated (as if, the force determines the direction of movement of the neuron lying on the rubber band). As the network evolves, the neurons (parameter vectors) approximate the convex-hull more and more accurately. The scheme can be applied to find the convex-hull of a planar set of circles or ellipses or a mixture of the two. Some properties related to the evolution of the algorithm are also presented.     

Pharmacokinetic analysis of polyamide nucleic-acid-cell penetrating peptide conjugates targeted against HIV-1 transactivation response element

We have demonstrated that polyamide nucleic acids complementary to the transactivation response (TAR) element of HIV-1 LTR inhibit HIV-1 production when transfected in HIV-1 infected cells. We have further shown that anti-TAR PNA (PNA(TAR)) conjugated with cell-penetrating peptide (CPP) is rapidly taken up by cells and exhibits strong antiviral and anti-HIV-1 virucidal activities. Here, we pharmacokinetically analyzed (125)I-labeled PNA(TAR) conjugated with two CPPs: a 16-mer penetratin derived from antennapedia and a 13-mer Tat peptide derived from HIV-1 Tat. We administered the (125)I-labeled PNA(TAR)-CPP conjugates to male Balb/C mice through intraperitoneal or gavage routes. The naked (125)I-labeled PNA(TAR) was used as a control. Following a single administration of the labeled compounds, their distribution and retention in various organs were monitored at various time points. Regardless of the administration route, a significant accumulation of each PNA(TAR)-CPP conjugate was found in different mouse organs and tissues. The clearance profile of the accumulated radioactivity from different organs displayed a biphasic exponential pathway whereby part of the radioactivity cleared rapidly, but a significant portion of it was slowly released over a prolonged period. The kinetics of clearance of individual PNA(TAR)-CPP conjugates slightly varied in different organs, while the overall biphasic clearance pattern remained unaltered regardless of the administration route. Surprisingly, unconjugated naked PNA(TAR) displayed a similar distribution and clearance profile in most organs studied although extent of its uptake was lower than the PNA(TAR)-CPP conjugates.     

Molecular signature of hypersaline adaptation: insights from genome and proteome composition of halophilic prokaryotes

Background  

Halophilic prokaryotes are adapted to thrive in extreme conditions of salinity. Identification and analysis of distinct macromolecular characteristics of halophiles provide insight into the factors responsible for their adaptation to high-salt environments. The current report presents an extensive and systematic comparative analysis of genome and proteome composition of halophilic and non-halophilic microorganisms, with a view to identify such macromolecular signatures of haloadaptation.     

Comparative analyses of codon and amino acid usage in symbiotic island and core genome in nitrogen-fixing symbiotic bacterium Bradyrhizobium japonicum

Genes involved in the symbiotic interactions between the nitrogen-fixing endosymbiont Bradyrhizobium japonicum, and its leguminous host are mostly clustered in a symbiotic island (SI), acquired by the bacterium through a process of horizontal transfer. A comparative analysis of the codon and amino acid usage in core and SI genes/proteins of B. japonicum has been carried out in the present study. The mutational bias, translational selection, and gene length are found to be the major sources of variation in synonymous codon usage in the core genome as well as in SI, the strength of translational selection being higher in core genes than in SI. In core proteins, hydrophobicity is the main source of variation in amino acid usage, expressivity and aromaticity being the second and third important sources. But in SI proteins, aromaticity is the chief source of variation, followed by expressivity and hydrophobicity. In SI proteins, both the mean molecular weight and mean aromaticity of individual proteins exhibit significant positive correlation with gene expressivity, which violate the cost-minimization hypothesis. Investigation of nucleotide substitution patterns in B. japonicum and Mesorhizobium loti orthologous genes reveals that both synonymous and non-synonymous sites of highly expressed genes are more conserved than their lowly expressed counterparts and this conservation is more pronounced in the genes present in core genome than in SI.