A novel pH- and time-dependent system for colonic drug delivery

A novel pH- and time-dependent delivery system was developed for delivering drugs to the colon. In vitro studies showed that this novel system could release the drug at a predetermined time, which was mainly controlled by the coating layers of the system. The delayed time of the press-coating layer was controlled by its erosion rate, which followed Hixson-Crowell equation. A proper selection of such factors as the viscosity grade of HPMC and tablet hardness, etc., can help reproduce the drug release profile as expected. The transit profiles in two healthy volunteers by gamma scintigraphy demonstrated that the tablets were able to pass through the stomach and small intestine intact and could safely reach the distal end of the small intestine, where the system began to release the drug contained in the core tablet. For both of the volunteers, disintegration of the tablets occurred in the ascending colon, which had highlighted the potential of this system for colonic drug delivery.     

Controlled release by permeability alteration of cationic ammonio methacrylate copolymers using ionic interactions

A multiparticulate drug delivery system was studied in which the drug release of a model drug theophylline could be modulated by interactions of ammonio methacrylate polymer and anions. The system consisted of a EUDRAGIT® NE coated anionic core, layered with drug and further layered with EUDRAGIT® RS. The effects of different anions like chloride, succinate, citrate, and acetate as well as the thickness of the polymer layers on the in vitro drug release were studied. It was seen that succinate and acetate anions had permeability enhancing effects and citrate and chloride anions had permeability retarding effects on the polymer. The results indicate that changing these variables would enable us to get a desired release profile and hence the proposed system could be a viable alternative to existing technologies for the development of a controlled drug delivery system.     

Synthesis and characterization of three novel amphiphilic dextran self-assembled micelles as potential drug delivery system

Three types of amphiphilic dextran derivatives were synthesized via the connection of different diamine compounds between the carboxyl group of stearic acid (SA) and aldehyde group of oxidized dextran. These three amphiphilic dextran derivatives self-assemble to form polymer micelles in aqueous medium. The critical micelle concentration depended on the graft ratio of SA, which ranged from 0.0700 to 0.158 mg mL^?1. These three amphiphilic dextran micelles can form typical core–shell structures of various sizes. Curcumin (Cur) was used as a model drug, and all amphiphilic micelle dextran derivatives had excellent drug loading capacity and drug encapsulation efficiency. The in vitro drug release from amphiphilic dextran derivatives/Cur micelles could be prolonged by adjusting the type of diamine compounds and composition of Cur content. These results show the superior properties of polymer micelles and suggest that these micelles are promising carriers for drug delivery systems.     

Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres

Objectives: Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon.

Methods: CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV.

Results: In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r²?=?0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p?p?Conclusions: Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.     

Interaction between anionic dyes and cationic flocculant P(AM-DMC) in synthetic solutions

Copolymer of acrylamide and 2-[(methacryloyloxy)ethyl]trimethylammonium chloride [P(AM-DMC)] is found to be effective to combine anionic dyes with strong aqueous solubility. This work aims mainly at revealing the interaction between anionic dyes and [P(AM-DMC)] by running jar test, spectra analysis and equilibrium dialysis experiments. The results show that P(AM-DMC) effectively decolorizes the tested strong water soluble anionic dyes, such as acidic, reactive and direct dyes, from their aqueous solutions under mild acidic and neutral conditions. Higher cationicity and optimal dose of flocculant P(AM-DMC) have to be used to achieve satisfactory and effective decolorization. Comparison of IR spectra of dye, flocculant P(AM-DMC) and the floc formed indicates chemical interaction occurred between sulfonic groups of dye and quaternary ammonium of flocculant. Plots of r-logC suggest cooperative interaction exists evidently for some dyes tested. Addition of KCl or urea reduces binding extent evidently, which shows the importance of electrostatic and hydrophobic interaction. Therefore the interaction between dyes tested and P(AM-DMC) might be controlled by hydrophobic, cooperative interaction and energetic interaction which includes chemical and electrostatic interactions.     

Investigation of fibroblast and keratinocyte cell-scaffold interactions using a novel 3D cell culture system

In this study we investigated the influence of fibre diameter and interfibre space in 3D scaffolds on cellular behaviour of human dermal fibroblasts and a human keratinocyte cell line (HaCaT cell). Electrospun aligned poly L-lactic acid fibres (2–10 μ m) were bound to form fibres with a broad range of diameters (2–120 μ m) and then constructed in a specifically designed 3D cell culture system. Human dermal fibroblasts were introduced to one end of the free-standing fibres using a fibrin clot and encouraged to ‘walk the plank’. Under these conditions it was observed that a minimum fibre diameter of 10 μ m for fibroblast adhesion and migration arose. A thin layer of electrospun viscose rayon scaffold fibres (diameter 30–50 μ m, pore size 50–300 μ m) was also constructed in the 3D cell culture system. After introduction to the scaffold using cells contained within a fibrin clot, fibroblasts were observed to stratify and also elongate between fibres in order to occupy voids. An interfibre span of up to 200 μ m was possible by a single fibroblast, but more commonly void distances were spanned by cellular multilayering. In contrast, HaCaT keratinocytes cultured under identical conditions using viscose rayon scaffolds occupied very much smaller void distances of 50–80 μ m predominantly by stratification.     

Effects of thermal neutron irradiation on some potential excipients for colonic delivery systems

Different excipients, which are currently being studied for colon delivery systems, were examined with respect to their stability toward neutron irradiation as a potential method of radiolabeling the formulations for γ-scintigraphic studies. Three different pectin and four different hydroxypropyl methylcellulose (HPMC) types, in addition to two types of polymethacrylate films, were exposed to 1, 2, and 3 min of thermal neutron irradiation in a flux of 1.1 × 10¹³ n cm^-2 s^-1. The physicochemical characteristics of pectins and HPMCs and the mechanical properties of the polymethacrylate films were examined after the radioactivity of the samples had declined to background levels. Methods included ultraviolet (UV) and Fourier transform infrared (FTIR) spectroscopy, pH measurements, loss on drying, thermogravimetric analysis (TGA), viscosimetry, gas chromatographic (GC) analysis of pectin monosaccharides, and tensile strength testing of the films. The results suggest that pectins and HPMCs undergo degradation, as expressed by a significant reduction in the dynamic and intrinsic viscosities of the samples. Generally, HPMCs were more sensitive than pectins to neutron irradiation. However, calcium pectinate proved to be the most sensitive among all the investigated polymers. Both polymethacrylate films (Eudragit® L and S) resisted loss of mechanical properties following 1 and 2 min of neutron irradiation, whereas irradiation for 3 min implied significant changes in the appearance and the mechanical properties of Eudragit L films. As a conclusion, neutron irradiation results in dose-dependent degradation of the investigated polysaccharides and polymethacrylates. The consequences on the in vitro behavior of a formulation containing such polymers are discussed.     

A mussel-inspired delivery system for enhancing self-healing property of epoxy coatings

Dopamine (DA),one type of mussel-inspired biological molecules with adhesive nature and corrosion inhibitor property,are often used to functionalize the surfaces of various materials.Herein,we report the application of polydopamine (PDA) microcapsules as novel nanocontainers for the purpose,loading corrosion inhibitor (benzotriazole) in its shell structure,and then were embedded into epoxy coatings to provide self-healing and anti-corrosion protection for carbon steel.Fast release of benzotriazole in acidic environment caused by local corrosion and the chelating effect of PDA-Fe3+ can synergistically promote the formation of protective film on bare steel surface,which endows coatings with self-healing func-tionality.Electrochemical impedance spectroscopy (EIS),local electrochemical impedance spectroscopy(LEIS),and spray tests were conducted to evaluate the active inhibition and corrosion resistance of the loaded coatings.The scratched coating with incorporation of nanocontainers presented better protection performance,exhibiting increased Ro (oxide layer resistance) and Rct (charge transfer resistance) during initial immersion periods.The EIS tests in long-term immersion were also performed to confirm the anti-corrosion effect of composited coatings.These results demonstrated that benzotriazole-decorated PDA capsules dramatically enhanced the self-healing properties and anti-corrosion performance of epoxy coatings with the synergistic help of PDA and benzotriazole.     

Synthesis of zeolite NaY in anionic, cationic and nonionic emulsions

Zeolite NaY has been first synthesized respectively in the anionic, cationic and nonionic emulsions. The emulsion systems can accelerate zeolite NaY crystallization and in some cases retard the growth of impurity. Compared to the conventional zeolite NaY synthesized in the absence of emulsion, the emulsion-mediated NaY samples show different morphologies, larger surface areas and higher pore volumes depending on the charge nature of the surfactants involved. In particular, the NaY sample synthesized in the nonionic emulsion system presents a hierarchical pore structure with the highest BET surface area of 646.85 m² g⁻¹. The increase of surface areas for the NaY products made in emulsion media is due to the removal of emulsion components occluded in the pore structures through calcination. These features of the NaY zeolites synthesized in emulsion media, such as various product morphologies and high surface areas, may bestow the materials unique catalytic properties in their potential applications.     

Investigation of the interface problem between high temperature superconductor and ionic conductors

The charge carriers transfer process across the interface between a superconductor and an ionic conductor, around T _c is investigated. Low temperature electrochemical measurements are carried out on the interfaces between different polycrystalline high-T_c superconductors (HTSC) and RbAg₄l₅ and Ag⁺ ion-conducting glass. The experiments cover a temperature range down to 10 K in the de-frequency range. Atransient technique in the time domain and electrochemical impedance spectroscopy (EIS) in the frequency domain are used to study the silver (Ag⁺) deposition as the Faradaic charge transfer process at that interface. The results show significant enhancement of the charge transfer observed around the critical temperature. This was indicated by either an admittance peak in the transient measurements or a corresponding decrease of the polarization resistance (R _p) in EIS measurements. This enhancement of the charge transfer is correlated to the formation of Cooper pairs at T T _c and interpreted on the basis of a band structure model as a quantumelectrochemical phenomenon with the tunnelling of Cooper pairs through the electrochemical double layer.     

Lipid-based nanocarrier for quercetin delivery: system characterization and molecular interactions studies

The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid–polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20?nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability.     

Electrokinetic behaviour and dispersion characteristics of ceramic powders with cationic and anionic polyelectrolytes

Three different ceramic powders, viz. alumina, zirconia and silicon nitride were dispersed using two polyelectrolytes, one cationic (Betz 1190) and the other anionic (Darvan-C). All powders examined during the study could be well dispersed only under conditions of polymer dosage and pH such that the working pH is at least 2 pH units away from the pH_IEP of the powder-dispersant combination. The shift in the isoelectric point (IEP) of the powders were determined through electro-acoustic measurements on 1% volume suspensions. Specific free energy of interaction were also computed using a model based on the electrical double layer theory of surfactant absorption. Certain trade names and company products are mentioned in the text or identified in illustrations in order to adequately specify the experimental procedure and equipment used. In no case does such identification imply recommendation or endorsement by the authors and their respective institutes nor does it imply that the products are necessarily the best available for the purpose.     

Slow release of ciprofloxacin from double potential drug delivery system

Psyllium polysaccharide is a bulk laxative and has been used for the treatment of constipation which is responsible for the diverticulitis. Ciprofloxacin is an antibiotic used for the microorganism infested in the diverticula. Hence, the functionalization of psyllium with polyvinyl alcohol (PVA) and poly(acrylamide) [poly(AAm)] will develop the drug delivery system (DDS) with potential for dual action for the treatment of diverticulitis, that is, by treating the constipation due to laxative action of psyllium and release of ciprofloxacin from DDS in controlled manner. The optimum conditions for the synthesis of hydrogels have been obtained as 42.21 × 10⁻² mol/L of AAm, 3% (w/v) of PVA, 32.43 × 10⁻³ mol/L of N,N′-methylenebisacrylamide (NN-MBA), 17.53 × 10⁻³ mol/L ammonium persulfate, and 1 g of psyllium. The characterization of the hydrogels has been carried out by SEMs, EDAX, FTIR, and swelling studies. Swelling and drug release studies have also been carried out to determine the mechanism of swelling of hydrogels and drug release from the drug loaded hydrogels. The release of the drug from the hydrogels occurred through Fickian diffusion mechanism in pH 2.2 and pH 7.4 buffer.     

Simultaneous separation of cationic and anionic proteins using zwitterionic surfactants in capillary electrophoresis

The zwitterionic surfactant Rewoteric AM CAS U forms a dynamic wall coating that prevents the adsorption of cationic proteins as well as suppresses the electroosmotic flow (EOF). Addition of polarizable anions to buffers containing this zwitterionic surfactant increases the once suppressed EOF to values nearing +3 x 10(-4) cm2/(V s). The retention of the EOF allows for the separation of analytes of widely different mobilities and is demonstrated by the simultaneous separation of cationic and anionic proteins. Using a buffer containing optimal amounts of the polarizable anion perchlorate and surfactant CAS U, the proteins lysozyme, ribonuclease A, alpha-chymotrypsinogen A, and myoglobin are separated in less than 15 min. Efficiencies as high as 1.5 million plates/m and recoveries greater than 91% are observed for proteins injected in distilled water. Migration time reproducibility is approximately 1% RSD within 1 day and approximately 3% RSD from day to day. The anionic and cationic proteins can be separated over a pH range of 5.5-9, all yielding good efficiencies.     

Novel combination of anionic and cationic polymethacrylate polymers for sustained release tablet preparation

The objectives of this study were to prepare and evaluate a novel sustained release tablet formulation using a binary mixture of polymethacrylate polymers: Eudragit E-100 (EE) and Eudragit L-100 (EL) in their salt forms. Tablets prepared using EE-citrate and EL-Na showed the highest degree of swelling among other combinations of EE and EL. The drug release rates were independent of the pH of the dissolution medium as the release profiles exhibited a continuous release pattern with no burst effect when changing the pH of the medium. These results, along with other test results, indicated the presence of an ionic interaction between both polymers when combined in the salt forms.     

TiO2/clinoptilolite composites for photocatalytic degradation of anionic and cationic contaminants

The present work aims to study the bulk and surface properties of the TiO₂/clinoptilolite composite on the crystalline structure, superficial area, bandgap energy, zeta potential, particle size distribution, and chemical composition; in order to analyze the effect of the clinoptilolite proportion in the photocatalytic degradation of pollutants. TiO₂/clinoptilolite composites were prepared by adding different mass proportions of clinoptilolite to a sol–gel bath containing TiCl₄ as the titania precursor. Surface charge studies explain the larger sensitivity to composite ratio observed in the photocatalytic degradation of anionic pollutants than in cationic dyes. An optimum TiO₂/clinoptilolite ratio of 90/10 was found to be the most efficient in terms of lower tendency to agglomeration, largest surface area, and increased crystallite size. Improvement in composite surface area occurs only at low clinoptilolite wt% and seems to be caused by lower agglomeration of nanometric TiO₂ and acid-induced porosity in the zeolite.     

Investigation of a novel freeze-thaw process for the production of drug delivery hydrogels

Poly(vinyl alcohol) (PVA) is a water-soluble, biocompatible and biodegradable polymer, which has been widely applied in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of PVA and comprising a blend of poly(vinyl alcohol) (PVA) with different concentrations of HCl, NaOH and NaCl are prepared by a freezing/thawing treatment of aqueous solutions. The structure and complexation of the electrolytes were studied by Fourier transform infrared (FTIR) spectroscopy. The mechanical properties were investigated using rheometery and the thermal transitions of the hydrogels were examined by modulated differential scanning calorimetry (MDSC). Freeze/thawed PVA gels containing NaOH showed overall enhanced swelling with increased mechanical strength over traditional gels prepared by chemical or irradiative crosslinking techniques. These novel physically cross-linked hydrogels show promise for a variety of biomedical and drug delivery applications.