Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled (proportional to time(-0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs.

Intermolecular interactions, charge-density distribution and the electrostatic properties of pyrazinamide anti-TB drug molecule: an experimental and theoretical charge-density study

An experimental charge-density analysis of pyrazinamide (a first line antitubercular drug) was performed using high-resolution X-ray diffraction data (sin theta/lambda)(max) = 1.1 angstrom(-1)] measured at 100 (2) K. The structure was solved by direct methods using SHELXS97 and refined by SHELXL97. The total electron density of the pyrazinamide molecule was modeled using the Hansen-Coppens multipole formalism implemented in the XD software. The topological properties of electron density determined from the experiment were compared with the theoretical results obtained from CRYSTAL09 at the B3LYP/6-31G** level of theory. The crystal structure was stabilized by N-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds, in which the N3-H3B center dot center dot center dot N1 and N3-H3A center dot center dot center dot O1 interactions form two types of dimers in the crystal. Hirshfeld surface analysis was carried out to analyze the intermolecular interactions. The fingerprint plot reveals that the N center dot center dot center dot H and O center dot center dot center dot H hydrogen-bonding interactions contribute 26.1 and 18.4%, respectively, of the total Hirshfeld surface. The lattice energy of the molecule was calculated using density functional theory (B3LYP) methods with the 6-31G** basis set. The molecular electrostatic potential of the pyrazinamide molecule exhibits extended electronegative regions around O1, N1 and N2. The existence of a negative electrostatic potential (ESP) region just above the upper and lower surfaces of the pyrazine ring confirm the pi-electron cloud.

Polyelectrolyte/silver nanocomposite multilayer films as multifunctional thin film platforms for remote activated protein and drug delivery

We demonstrate a nanoparticle loading protocol to develop a transparent, multifunctional polyelectrolyte multilayer film for externally activated drug and protein delivery. The composite film was designed by alternate adsorption of poly(allylamine hydrochloride) (PAH) and dextran sulfate (DS) on a glass substrate followed by nanoparticle synthesis through a polyol reduction method. The films showed a uniform distribution of spherical silver nanoparticles with an average diameter of 50 +/- 20 nm, which increased to 80 +/- 20 nm when the AgNO3 concentration was increased from 25 to 50 mM. The porous and supramolecular structure of the polyelectrolyte multilayer film was used to immobilize ciprofloxacin hydrochloride (CH) and bovine serum albumin (BSA) within the polymeric network of the film. When exposed to external triggers such as ultrasonication and laser light the loaded films were ruptured and released the loaded BSA and CH. The release of CH is faster than that of BSA due to a higher diffusion rate. Circular dichroism measurements confirmed that there was no significant change in the conformation of released BSA in comparison with native BSA. The fabricated films showed significant antibacterial activity against the bacterial pathogen Staphylococcus aureus. Applications envisioned for such drug-loaded films include drug and vaccine delivery through the transdermal route, antimicrobial or anti-inflammatory coatings on implants and drug-releasing coatings for stents. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Charge density distribution and electrostatic interactions of ethionamide: an inhibitor of the enoyl acyl carrier protein reductase (inhA) enzyme of Mycobacterium tuberculosis

An experimental charge density analysis of an anti-TB drug ethionamide was carried out from high resolution X-ray diffraction at 100 K to understand its charge density distribution and electrostatic properties. The experimental results were validated from periodic theoretical charge density calculations performed using CRYSTAL09 at the B3LYP/6-31G** level of theory. The electron density rho(bcp)(r) and the Laplacian of electron density del(2)(rho bcp)(r) of the molecule calculated from both the methods display the charge density distribution of the ethionamide molecule in the crystal field. The electrostatic potential map shows a large electropositive region around the pyridine ring and a large electronegative region at the vicinity of the thiol atom. The calculated experimental dipole moment is 10.6D, which is higher than the value calculated from theory (8.2D). The topological properties of C-H center dot center dot center dot S, N-H center dot center dot center dot N and N-H center dot center dot center dot S hydrogen bonds were calculated, revealing their strength. The charge density analysis of the ethionamide molecule determined from both the experiment and theory gives the topological and electrostatic properties of the molecule, which allows to precisely understand the nature of intra and intermolecular interactions.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

A new load distribution strategy for linear network with communication delays

In this paper, we propose a new load distribution strategy called `send-and-receive' for scheduling divisible loads, in a linear network of processors with communication delay. This strategy is designed to optimally utilize the network resources and thereby minimizes the processing time of entire processing load. A closed-form expression for optimal size of load fractions and processing time are derived when the processing load originates at processor located in boundary and interior of the network. A condition on processor and link speed is also derived to ensure that the processors are continuously engaged in load distributions. This paper also presents a parallel implementation of `digital watermarking problem' on a personal computer-based Pentium Linear Network (PLN) topology. Experiments are carried out to study the performance of the proposed strategy and results are compared with other strategies found in literature.

An Efficient Load Distribution Strategy for a Distributed Linear Network of Processors with Communication Delays

In this paper, we present an improved load distribution strategy, for arbitrarily divisible processing loads, to minimize the processing time in a distributed linear network of communicating processors by an efficient utilization of their front-ends. Closed-form solutions are derived, with the processing load originating at the boundary and at the interior of the network, under some important conditions on the arrangement of processors and links in the network. Asymptotic analysis is carried out to explore the ultimate performance limits of such networks. Two important theorems are stated regarding the optimal load sequence and the optimal load origination point. Comparative study of this new strategy with an earlier strategy is also presented.

Integral Formulation of the Problem of Current Distribution in Compulsator Wires of Electromagnetic Launchers and Railguns

Compulsators are power sources of choice for use in electromagnetic launchers and railguns. These devices hold the promise of reducing unit costs of payload to orbit. In an earlier work, the author had calculated the current distribution in compulsator wires by considering the wire to be split into a finite number of separate wires. The present work develops an integral formulation of the problem of current distribution in compulsator wires which leads to an integrodifferential equation. Analytical solutions, including those for the integration constants, are obtained in closed form. The analytical solutions present a much clearer picture of the effect of various input parameters on the cross-sectional current distribution and point to ways in which the desired current density distribution can be achieved. Results are graphically presented and discussed, with particular reference to a 50-kJ compulsator in Bangalore. Finite-element analysis supports the results.

Spatial distribution of aerosol black carbon over India during pre-monsoon season

Aerosol black carbon (BC) mass concentrations ([BC]), measured continuously during a multi-platform field experiment, Integrated Campaign for Aerosols gases and Radiation Budget (ICARB, March-May 2006), from a network of eight observatories spread over geographically distinct environments of India, (which included five mainland stations, one highland station, and two island stations (one each ill Arabian Sea and Bay of Bengal)) are examined for their spatio-temporal characteristics. During the period of study, [BC] showed large variations across the country, with values ranging from 27 mu g m(3) over industrial/urban locations to as low as 0.065 mu g m(-3) over the Arabian Sea. For all mainland stations, [BC] remained high compared to highland as well as island stations. Among the island stations, Port Blair (PBR) had higher concentration of BC, compared to Minicoy (MCY), implying more absorbing nature of Bay of Bengal aerosols than Arabian Sea. The highland station Nainital (NTL), in the central Himalayas, showed low values of [BC], comparable or even lower than that of the island station PBR, indicating the prevalence of cleaner environment over there. An examination of the changes in the mean temporal features, as the season advances from winter (December-February) to pre-monsoon (March-May), revealed that: (a) Diurnal variations were pronounced over all the mainland stations, with all afternoon low and a nighttime high: (b) At the islands, the diurnal variations, though resembled those over the mainlands, were less pronounced; and (c) In contrast to this, highland station showed an opposite pattern with an afternoon high and a late night or early morning low. The diurnal variations at all stations are mainly caused by the dynamics of local Atmospheric Boundary Layer (ABL), At the entire mainland as well as island stations (except HYD and DEL), [BC] showed a decreasing trend from January to May, This is attributed to the increased convective mixing and to the resulting enhanced vertical dispersal of species in the ABL. In addition, large short-period modulations were observed at DEL and HYD, which appeared to be episodic, An examination of this in the light of the MODIS-derived fire count data over India along with the back-trajectory analysis revealed that advection of BC from extensive forest fires and biomass-burning regions upwind were largely responsible for this episodic enhancement in BC at HYD and DEL.

Microstructural evolution and mechanical characteristics in nanocrystalline nickel with a bimodal grain-size distribution

An attractive microstructural possibility for enhancing the ductility of high-strength nanocrystals is to develop a bimodal grain-size distribution, in which the fine grains provide strength, and the coarser grains enable strain hardening. Annealing of nanocrystalline Ni over a range of temperatures and times led to microstructures with varying volume fractions of coarse grains and a change in texture. Tensile tests revealed a drastic reduction in ductility with increasing volume fraction of coarse grains. The reduction in ductility may be related to the segregation of sulphur to grain boundaries.

Optimum Evaluation of Reactive Power Requirements in Power Distribution-Systems

This paper presents three methodologies for determining optimum locations and magnitudes of reactive power compensation in power distribution systems. Method I and Method II are suitable for complex distribution systems with a combination of both radial and ring-main feeders and having different voltage levels. Method III is suitable for low-tension single voltage level radial feeders. Method I is based on an iterative scheme with successive powerflow analyses, with formulation and solution of the optimization problem using linear programming. Method II and Method III are essentially based on the steady state performance of distribution systems. These methods are simple to implement and yield satisfactory results comparable with the results of Method I. The proposed methods have been applied to a few distribution systems, and results obtained for two typical systems are presented for illustration purposes.

Distribution of black nodes at various levels in a linear quadtree

The distribution of black leaf nodes at each level of a linear quadtree is of significant interest in the context of estimation of time and space complexities of linear quadtree based algorithms. The maximum number of black nodes of a given level that can be fitted in a square grid of size 2n × 2n can readily be estimated from the ratio of areas. We show that the actual value of the maximum number of nodes of a level is much less than the maximum obtained from the ratio of the areas. This is due to the fact that the number of nodes possible at a level k, 0≤k≤n − 1, should consider the sum of areas occupied by the actual number of nodes present at levels k + 1, k + 2, …, n − 1.

Distribution of phosphorus and oxygen between liquid steel and basic oxygen steelmaking slag

The efficiency of dephosphorisation is governed by the thermodynamic behaviour of phosphorus and oxygen in molten metal, and P2O5 and FeO in slag. The equilibrium distribution of phosphorus and oxygen, for a wide range of chemical compositions simulating the evolution of slag composition during a typical BOF blow, has been experimentally determined. A mathematical model for estimation of the activity coefficients, as a function of the chemical composition, was also attempted.