Novel thermo‐responsive semi‐interpenetrating network microspheres of gellan gum‐poly(N‐isopropylacrylamide) for controlled release of atenolol

Thermoresponsive microspheres of gellan gum‐poly(N‐isopropylacrylamide), i.e., GG‐P(NIPAAm) semi‐interpenetrating polymer networks (semi‐IPNs) have been prepared by ionic crosslinking and used to study the controlled release (CR) of atenolol (ATL), an antihypertensive drug. Interaction of the drug with polymers was studied by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) was used to confirm the polymorphism and molecular level dispersion of ATL. Scanning electron microscopy (SEM) indicated spherical nature and smooth surfaces of the microspheres with some debris attached on their surfaces. Mean particle size measured by laser light diffraction ranged between 34 and 76 μm. Equilibrium swelling performed at 25°C and 37°C in pH 7.4 phosphate buffer exhibited thermoresponsive nature of the polymers. In vitro drug release performed at 25°C and 37°C indicated temperature‐dependency of ATL release, which was extended up to 12 h. In vitro release profiles at both the temperatures confirmed thermoresponsive nature of the polymers giving pulsatile trends. The % cumulative release data have been fitted to an empirical equation to estimate transport parameters and to understand the nature of drug release. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Molecular characterization of a broad selectivity neutral solute channel

In all living cells, coordination of solute and water movement across cell membranes is of critical importance for osmotic balance. The current concept is that these processes are of distinct biophysical nature. Here we report the expression cloning of a liver cDNA encoding a unique promiscuous solute channel (AQP9) that confers high permeability for both solutes and water. AQP9 mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl-, and deprotonated monocarboxylates are excluded. The properties of AQP9 define a new evolutionary branch of the major intrinsic protein family of aquaporin proteins and describe a previously unknown mechanism by which a large variety of solutes and water can pass through a single pore, enabling rapid cellular uptake or exit of metabolites with minimal osmotic perturbation.     

Structural,Dielectric and AC Conductivity of Multicomponent Borotellurite Glasses

Glass Physics and Chemistry - Structural, dielectric and conductivity of multicomponent borotellurite glasses have been thorougly investigated. Noncrystallinity confirmed through XRD and structural...     

Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator

CFTR is a cyclic AMP (cAMP)-activated chloride (Cl-) channel and a regulator of outwardly rectifying Cl- channels (ORCCs) in airway epithelia. CFTR regulates ORCCs by facilitating the release of ATP out of cells. Once released from cells, ATP stimulates ORCCs by means of a purinergic receptor. To define the domains of CFTR important for Cl- channel function and/or ORCC regulator function, mutant CFTRs with N- and C-terminal truncations and selected individual amino acid substitutions were created and studied by transfection into a line of human airway epithelial cells from a cystic fibrosis patient (IB3-1) or by injection of in vitro transcribed complementary RNAs (cRNAs) into Xenopus oocytes. Two-electrode voltage clamp recordings, 36Cl- efflux assays, and whole cell patch-clamp recordings were used to assay for the Cl- channel function of CFTR and for its ability to regulate ORCCs. The data showed that the first transmembrane domain (TMD-1) of CFTR, especially predicted alpha-helices 5 and 6, forms an essential part of the Cl- channel pore, whereas the first nucleotide-binding and regulatory domains (NBD1/R domain) are essential for its ability to regulate ORCCs. Finally, the data show that the ability of CFTR to function as a Cl- channel and a conductance regulator are not mutually exclusive; one function could be eliminated while the other was preserved.     

The complexity of scheduling for data cache optimization

The performance of the memory hierarchy, and in particular the data cache, can significantly impact program execution speed. Thus, instruction reordering to minimize data cache misses is an important consideration for optimizing compilers. In this paper, we prove that the problem of instruction reordering for data cache miss minimization belongs to the class of NP-complete problems. The framework that we develop for the proof exposes the symbiotic relationship among the references to the cache. This symbiosis exists because a single cache reference lengthens the life span of its neighbors in the cache, and thus provides opportunity for additional cache hits through reference to the neighbors. We present a greedy heuristic designed to exploit this symbiotic relationship to improve data cache performance for general-purpose programs. Experiments with a prototype implementation of the heuristic show that we can improve data cache performance in many cases.     

Experimental simulation of large-scale bioreaetor environments using a Monte Carlo method

Cells grown in production-scale stirred bioreactors experience fluctuating concentrations due to local variations in supply and consumption of oxygen and nutrients. A new method for studying the effects of fluctuations in local conditions on growth and productivity of cells was developed using a Monte Carlo approach to simulate circulation within a fermenter. A small fermenter was driven through cycles of aeration and feeding, with the time of each cycle controlled by a Monte Carlo method to give a log-normal distribution. Experiments with Monte Carlo supply of air to batch and fed-batch cultures of Saccharomyces cerevisiae showed that the method gave reproducible results which were different from both periodic cycling and continuous supply. When substrate was provided to a fed-batch culture of S. cerevisiae according to the Monte Carlo method, the yields of biomass were higher than experiments with continuous feeding or periodic feeding.     

Preparation and evaluation of novel blend microspheres of poly(lactic‐co‐glycolic)acid and pluronic F68/127 for controlled release of repaglinide

The objective of the present work was to study the release behavior of plain and blend microspheres (MS) of PLGA and Pluronic F68/127. In this study, a novel blend MS of poly(D ,L ‐lactic‐co‐glycolic acid) (PLGA) and Pluronic F68/127 (PLF68/127) were prepared by the emulsion–solvent evaporation method. Repaglinide, an antidiabetic drug with a very short half‐life, was successfully encapsulated into the blend MS. Various formulations were prepared by varying the ratio of PLGA and PLF68/127. Drug encapsulation up to 91% was achieved as measured by UV spectroscopy. Scanning electron microscopy showed that MS have smooth surfaces even after incorporation of PLF68/127. Particle size, as measured by using laser light scattering technique, gave an average size ranging from 12 to 47 μm. Differential scanning calorimetry (DSC) was performed to understand the crystalline nature of the drug after encapsulation into MS. DSC revealed the crystalline dispersion in the polymer matrix. In vitro release experiments performed in simulated intestinal fluid, indicated the dependence of release rate on the amount of PLF68/127 present in the MS; slow release was extended up to 153 h. Release data have been fitted to an empirical equation to compute the diffusional exponent (n), which indicated that the release mechanism to be non‐Fickian type. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

The cystic fibrosis transmembrane conductance regulator and ATP

The purpose of this study was to monitor changes in preoperative routines following recommendations given in 1989 by the Swedish Council on Technology Assessment and by the Swedish Consensus Conference on Preoperative Routines, both suggesting a more individualized utilization of preoperative testing. This was a multicenter, prospective, repetitive study conducted at seven Swedish hospitals providing surgical care. The subjects included all patients presenting at the operating theaters for surgical interventions requiring general or regional anesthesia. The main outcome measures were the frequency of reports of performed preoperative ECG, chest x-ray, and analysis of serum concentration of potassium. Before general recommendations were issued in 1989, 47% of the patients had had a preoperative ECG, 26% had had a chest x-ray, and in 61% serum potassium concentration had been measured. In 1991 these frequencies had been reduced by 5, 6, and 9 percentage points, respectively (all figures given standardized for age and sex). Large differences were found between individual hospitals. Although recommendations suggesting a more restrictive and individualized utilization of preoperative testing have sparked important revisions in Swedish hospitals, there seems to be substantial potential remaining for further reduction of perfunctory use of preoperative screening.     

Synthesis and characterization of methoxypolyethyleneglycol and lauric acid grafted novel polyurethanes for controlled release of nifedipine

Novel polyurethanes (PUs) grafted with methoxypolyethyleneglycol (mPEG) and lauric acid (LA) were synthesized by solution polymerization using dibutyl tin dilaurate as a catalyst, taking different molar ratios of LA‐trimethylol propane (LA‐TMP) with respect to mPEG‐trimethylol propane (mPEG‐TMP). The polymers obtained were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography to confirm, respectively, the PU formation and molecular weight. Moderate molecular‐weight PUs were obtained, and nifedipine (NFD)‐loaded microspheres were prepared by solvent evaporation method. The size of the microspheres as measured by laser light scattering technique ranged between 10 and 50 μm. An increase in the size of particles was observed with an increasing molar ratio of mPEG‐TMP with respect to LA‐TMP. The % encapsulation efficiency was found to vary between 65 and 92. The surface morphology of microspheres as studied by scanning electron microscopy revealed the spherical nature of the particles with wrinkles on their surfaces. Crystalline nature of the drug in the microspheres after loading was studied by X‐ray diffraction technique. The release of NFD through the matrix microspheres was investigated in pH‐7.4 phosphate buffer. An increase in release rate was observed with increasing molar ratio of mPEG‐TMP with respect to LA‐TMP. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Synthesis,characterization and evaluation of novel methoxypolyethyleneglycol‐ grafted‐ poly(ester‐urethane)s for controlled release of repaglinide

Novel biodegradable aliphatic poly(ester‐urethane)s (PEUs) based on polycaprolactone diol (PCL) and methoxypolyethyleneglycol grafted onto trimethylol propane (mPEG‐g‐TMP) were synthesized by solution polymerization technique and characterized using a variety of techniques. Microspheres ranging in size from 7 to 25 μm were prepared by the solvent evaporation technique and loaded with repaglinide up to 71 to 96%. Increasing molar ratios of mPEG‐g‐TMP propane with respect to polycaprolactone diol gave increase in particle size along with increase in % encapsulation efficiency. Surface morphology and spherical nature of the microspheres were confirmed by scanning electron microscopy (SEM). The release of repaglinide varied, depending upon the molar ratios of mPEG‐g‐TMP moieties with respect to PCL. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009