Methylated N-(4-N,N-Dimethylaminobenzyl) Chitosan, a Novel Chitosan Derivative, Enhances Paracellular Permeability Across Intestinal Epithelial Cells (Caco-2)

The aim of this study was to investigate the effect of methylated N-(4-N,N-dimethylaminobenzyl) chitosan, TM-Bz-CS, on the paracellular permeability of Caco-2 cell monolayers and its toxicity towards the cell lines. The factors affecting epithelial permeability, e.g., degree of quaternization (DQ) and extent of dimethylaminobenzyl substitution (ES), were evaluated in intestinal cell monolayers of Caco-2 cells using the transepithelial electrical resistance and permeability of Caco-2 cell monolayers, with fluorescein isothiocyanate dextran 4,400 (FD-4) as a model compound for paracellular tight-junction transport. Cytotoxicity was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability assay. The results revealed that, at pH 7.4, TM-Bz-CS appeared to increase cell permeability in a concentration-dependent manner, and this effect was relatively reversible at lower doses of 0.05–0.5 mM. Higher DQ and the ES caused the permeability of FD-4 to be higher. The cytotoxicity of TM-Bz-CS depended on concentration, %DQ, and %ES. These studies demonstrated that this novel modified chitosan has potential as an absorption enhancer.     

Microencapsulation by Spray Coagulation of Diltiazem HCl in Calcium Alginate-Coated Chitosan

The aim of this work was to develop a procedure for encapsulation of diltiazem HCl by spray coagulation. Factors affecting the formulations such as the effect of NaCl on the solubility of diltiazem in alginate solution, surface tension, pH, viscosity of the coagulation medium, and the effect of drug load on drug release were studied. The drug load was increased substantially from 10 up to 320 mg/mL by adding 1.2% w/v NaCl in 1% w/v alginate solution. More stable microcapsules were obtained at pH 4.6 (acetate buffer) than at a pH 2.8 (lactic acid), and the microencapsulation process was favored by the type of chitosan that produced low turbidity and viscosity in the coagulation medium. A dose of 50 mg/mL of diltiazem HCl, 1.2% w/v NaCl, and chitosan CS allowed higher amount of drug to be encapsulated. The high water solubility of diltiazem HCl leads to fast release from the microcapsules.     

Formulation Variables Influencing Drug Release from Layered Matrix System Comprising Chitosan and Xanthan Gum

The purpose of this study was to investigate the formulation variables influencing the drug release from the layered tablets containing chitosan and xanthan gum as matrix component. Increasing the amount of lactose could diminish pH sensitive release behavior of these matrix tablets. Effect of formulation variables on drug release from the prepared three-layered matrix tablets was investigated. The amount of drug loading did not affect the drug release which was influenced by the hydrodynamic force and the matrix composition. An increase in stirring rate correspondingly increased the release rate. Moreover, incorporation of soluble diluents in core or barrier could enhance the drug release. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi’s and zero order) was carried out to study the drug release mechanism. Most dissolution profiles of the prepared three-layered tablets provided a better fit to zero order kinetic than to first order kinetic and Higuchi’s equation.     

Optical investigation of the electron transfer protein azurin-gold nanoparticle system

The hybrid system obtained by conjugating the protein azurin, which is a very stable and well-described protein showing a unique interplay among its electron transfer and optical properties, with 20-nm sized gold nanoparticles has been investigated. Binding of azurin molecules to gold nanoparticle surface results in the red shift of the nanoparticle resonance plasmon band and in the quenching of the azurin single tryptophan fluorescence signal. These findings together with the estimate of the hydrodynamic radius of the composite, obtained by means of Dynamic Light Scattering, are consistent with the formation of a monolayer of protein molecules, with preserved natural folding, on nanoparticle surface. The fluorescence quenching of azurin bound molecules is explained by an energy transfer from protein to metal surface and it is discussed in terms of the involvement of the Az electron transfer route in the interaction of the protein with the nanoparticle.     

About mechanism of chitosan cross-linking with glutaraldehyde

The regularities of the reaction of aminopolysaccharide chitosan with glutaraldehyde (GA) have been considered. The equilibrium forms of GA in water have been thoroughly studied by NMR spectroscopy. It has been established that at pH 5.6, the exchange of the protons of O=CHCH₂ groups for deuterium occurs, indicating the presence of an anion, a product of the first stage of the aldol reaction; at pH > 7.2, the formation of the products of an aldol reaction and aldol condensation takes place. The kinetics of the reaction between the amino groups of chitosan and GA, the kinetics of gel formation in chitosan solutions in the presence of GA, and the kinetics of changes in the rigidity of gels formed have been studied by UV spectroscopy. IR spectra of cross-linked chitosan have been obtained. It has been shown that chitosan catalyzes the polymerization of GA to form irregular products; in this process, the length of oligomeric chains in modified or cross-linked chitosan and the concentration of conjugated bonds increase with the GA concentration and pH of the reaction medium.     

Electrochemical nitrite biosensor based on the immobilization of hemoglobin on an electrode modified by multiwall carbon nanotubes and positively charged gold nanoparticle

The report is on an electrochemical biosensor with remarkably improved sensitivity toward nitrite. In this strategy, positively charged gold nanoparticle (PCNA) is used in combination with multiwall carbon nanotubes (MWCNT) by electrostatic adsorption for fabricating PCNA/MWCNT films. Then hemoglobin (Hb) biocatalyst will easily be attached to the surface of the combination films aforementioned. After that, the Hb/PCNA films are immobilized onto the Hb/PCNA/MWCNT films through layer-by-layer assembly technique. The (Hb/PCNA)₂/MWNT/GC electrode thus prepared exhibits enhanced electrocatalytic behavior to the reduction of nitrite at −0.10 V versus SCE in 0.05 M H₂SO₄ solution_. On condition of the low detecting potential and low pH, interference caused by direct electrochemical oxidation or oxidizable substances can be prevented. Therefore, the modified electrode shows fast response time, very high sensitivity, good selectivity and stability. The current response of the sensor increases linearly with nitrite concentration from a range of 3.6 × 10⁻⁶ to 3.0 × 10⁻³ M with a detection limit(S /N = 3) of 9.6 × 10⁻⁷ M.     

Fabrication of Biomimetic Water Strider Legs Covered with Setae

Water striders have remarkable water-repellent legs that enable them to stand effortlessly and move quickly on water.Fluidphysics indicates this feature is due to a surface-tension effect caused by the special hierarchical structure of the legs,which arecovered with a large number of inclined setae with fine nanogrooves inducing water resistance.This inspires us to fabricatespecial water-repellent structure on functional surfaces through the cooperation between the surface treatment and the surfacemicro-and nanostructures,which may bring great advantages in a wide variety of applications.In this paper we present aprocedure for fabricating biomimetic water strider legs covered with setae using Polycarbonate Track-Etched(PCTE)membranesas templates.By choosing appropriate membrane lengths,diameters,pitches and densities of the setae,the biomimeticlegs can be fabricated conveniently and at a low cost.Furthermore we investigated the relationship between stiffness of themolding materials,high aspect ratio and density,which affect the fidelity of fabrication and self adhesion,to optimize thestability of setae.The knowledge we gained from this study will offer important insights into the biomimetic design and fabricationof water strider setae.     

Preparation, characterization, and antibacterial activity of oleic acid-grafted chitosan oligosaccharide nanoparticles

An oleic acid-grafted chitosan oligosaccharide (CSO-OA) with different degrees of amino substitution (DSs) was synthesized by the 1-ethyl-3-(3-dimethylami-nopropyl) carbodiimide (EDC)-mediated coupling reac-tion. Fourier transform infrared spectroscopy (FT-IR) suggested the formation of an amide linkage between amino groups of chitosan oligosaccharide and carboxyl groups of oleic acid. The critical aggregation concentra-tions (CACs) of CSO-OA with 6%, 11%, and 21% DSs were 0.056, 0.042, and 0.028mg·mL-1, respectively. Nanoparticles prepared with the sonication method were characterized by means of transmission electron micro-scopy (TEM) and Zetasizer, and the antibacterial activity against Escherichia coli and Staphylococcus aureus was investigated. The results showed that the CSO-OA nanoparticles were in the range of 60-200 nm with satisfactory structural integrity. The particle size slightly decreased with the increase of DS of CSO-OA. The antibacterial trial showed that the nanoparticles had good antibacterial activity against E. coli and S. aureus.     

Development and Characterization of 99mTc-timolol Maleate for Evaluating Efficacy of In Situ Ocular Drug Delivery System

In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive technique. For scintigraphy study, the drug timolol maleate was radiolabeled ^99mTc by direct labeling method using SnCl₂·2H₂O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug (^99mTc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images and the time–activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed formulation was also checked by hen’s egg chorioallantoic membrane test and formulation was found to be practically nonirritant. The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner.     

Chitosan–Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin

The different approaches for targeting orally administered drugs to the colon include coating with pH-dependent polymers, design of time-release dosage forms, and the utilization of carriers that are degraded exclusively by colonic bacteria. The aim of the present study was to develop a single unit, site-specific drug formulation allowing targeted drug release in the colon. Matrix tablets were prepared by wet granulation using cross-linked chitosan (ChI) and chondroitin sulfate (ChS) polysaccharides as binder and carrier. ChS was used to form polyelectrolyte complexes (PEC) with ChI, and its potential as a colon-targeted drug carrier was investigated. Indomethacin was used as a model drug. The ChI and ChS PEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction studies (XRD). The matrix tablets were tested in vitro for their suitability as colon-specific drug delivery systems. FTIR demonstrated that the PEC forms through an electrostatic interaction between the protonated amine (NH₃⁺) group of ChI with the free carboxylate (COO⁻) group and sulfate (SO₄²⁻) group of ChS. DSC and XRD indicated that the PEC has different thermal characteristics from ChI or ChS. The dissolution data demonstrates that the dissolution rate of the tablet is dependent upon the concentration of polysaccharide used as binder and matrix and time of cross-linking. The study confirmed that selective delivery of indomethacin to the colon can be achieved using cross-linked ChI and ChS polysaccharides.