Tuberculosis chemotherapy: current drug delivery approaches

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance

chromium(VI) ions

The polyethyleneglycolmethacrylate-co-vinylimidazole (PEGMA-VI) copolymers, that can be used in heavy metal removal applications, were synthesized and characterized; and their use as sorbents in heavy metal removal was investigated. It was determined that the ligand vinylimidazole was successfully inserted into the polymer structure. Then, chromium (Cr(VI)) and nickel (Ni(II)) ions were used as model species to investigate the usability of the obtained microspheres in heavy metal removal. The effects of pH of the adsorption medium, initial concentration of the metal ions and VI content of PEGMA-VI microspheres were investigated as the effective parameters on the adsorption capacities of the microspheres. The adsorption rate of the microspheres was also investigated for determination of the optimum adsorption time which is the required time for maximum adsorption capacity. The adsorption capacities under optimum conditions were also determined. The order of adsorption affinities of PEGMA-VI microspheres with respect to the used metals was determined by competitive adsorption studies. According to the obtained results, the highest adsorption affinity of the PEGMA-VI microspheres was towards Cr(VI) ions, the adsorption affinity was less for Ni(II) and the least affinity was towards Cu(II) ions. The adsorption-desorption studies showed that the microspheres were reusable without a significant decrease in the ion adsorption capacities. (C) 2009 Elsevier B.V. All rights reserved

removal

Polyethyleneglycolmethacrylate (PEGMA) and vinylimidazole (VI) were used in order to obtain microspheres of PEGMA-VI copolymers that can be used in heavy metal removal applications. The obtained copolymers were characterized and their use as sorbents in heavy metal removal was investigated. In the first part of the study, PEGMA-VI microspheres were prepared by suspension polymerization method. The obtained swellable microspheres with 10-50 mu m average diameter did not have permanent porosity according to the morphological and physicochemical determinations. The sizes of microspheres became smaller with increasing VI and cross-linker ethyleneglycoldimethacrylate (EGDMA) contents and increasing agitation rate. The VI content, EGDMA ratio, pH and ionic strength were determined as the effective parameters on the swelling behavior of PEGMA-VI microspheres. In the second part of the study, Cu(II) ions were used as a model species in order to investigate the usability of the obtained PEGMA-VI microspheres in heavy metal removal. Adsorption capacities under optimum conditions were determined. The Cu(II) ion adsorption capacity increased by increasing the initial Cu(II) ion concentration, and it reached the maximum value (i.e., 30 mg Cu(II)/g PEGMA-VI microspheres) at 400 mg Cu(II)/L initial Cu(II) ion concentration under the determined optimum conditions. Microspheres were found to be reusable after desorption for several times. (C) 2008 Elsevier B.V. All rights reserved

thermosensitive copolymers

Thermosensitive copolymers of N-isopropylacrylamide (NIPA) and N-acryloxysuccinimide (NASI) were obtained by solution polymerization using azobisisobutyronitrile as the initiator in a tetrahydrofuran-toluene mixture at 65degreesC. A boronic acid-carrying ligand, m-aminophenylboronic acid (APBA) was covalently attached to the thermosensitive copolymer via the reaction between amino and succinimide groups. APBA-coupled thermosensitive copolymer exhibited both temperature and pH sensitivity. Thermally reversible phase transitions were observed both in the acidic and alkaline pH region for the APBA-modified copolymers obtained with different NASI feed concentrations. In our study, ribonucleic acid (RNA) was selected as a biomolecule having reactive groups which could potentially interact with the boronic acid functionality. The response of boronic acid-carrying thermosensitive copolymer against RNA was investigated in aqueous media in the pH range 4-9. In the acidic pH region, an increase was observed in the lower critical solution temperature (LCST) of the APBA-coupled thermosensitive copolymer with increasing RNA concentration. However, LCST decreased with increasing RNA concentration at both neutral and alkaline pH values. The LCST of the APBA-attached copolymer varied linearly with the RNA concentration at pH of 3, 4 and 7. (C) 2003 Society of Chemical Industry

A new temperature-sensitive polymer: Poly(ethoxypropylacrylamide)

In this study, a new temperature sensitive polymer was obtained by the solution polymerization of ethoxypropyl-acrylamide. The monomer, N-(3-ethoxypropyl)-acrylamide was synthesized by the nucleophilic substitution reaction of 3-ethoxy-propylamine and acryloyl chloride. The solution polymerization was performed in ethanol at 70 degrees C, by using azobisizobutyronitrile as the initiator. Poly(N-(3-ethoxypropyl)acrylamide), PEPA, exhibited a reversible phase transition by the temperature. The effects of polymer and salt concentrations on the lower critical solution temperature, (LCST) behaviour were investigated. LCST was found to be strongly dependent on the polymer concentration. The dynamic light scattering (DLS) measurements confirmed the formation of aggregates by the association of nucleated polymer chains at the temperatures higher than LCST. However an unusual behaviour, a marked decrease in the hydrodynamic diameter by the increasing PEPA concentration was observed below the LCST. The effect of salt concentration on the critical flocculation temperature of PEPA was reasonably similar to poly(isopropylacrylamide), PNIPA. In the ethanol-water media, the reversible phase transition behaviour was observed up the ethanol concentration of 30% v/v. This study indicated that PEPA was a new alternative thermally reversible material for PNIPA. With respect to the well-defined temperature-sensitive polymers like PNIPA, polymer concentration dependent LCST of PEPA can provide significant advantages in the applications like drug targeting, affinity separation and immobilization of bioactive agents. (c) 2005 Elsevier Ltd. All rights reserved

Gold and gold-palladium coated polypropylene grafts in a S-epidermidis wound infection model

WOS: 000235771200010PubMed: 16139304Background. The use of non-absorbable mesh grafts in both abdominal wall defects and inguinal hernias are impossible in the presence of contamination. This study was conducted for evaluation of the efficiencies of polypropylene mesh grafts coated with gold and palladium-gold. Materials and methods. Ten piece of 1 x 2 cm. of polypropylene mesh grafts were used in each group of naive, gold-coated, and palladium-gold-coated. The grafts were incubated in physiological saline buffered and 0.5 McFarland slime positive Staphylococcus epidermidis for 24 h. At intervals of 6,12,24,48, 72 h grafts were washed with saline and vortexed for 2 min in 2 ml of physiological saline. There were 100 mu l of samples of vortexed material incubated in blood agar and 24 h later, colony numbers were assessed. In the second part of study, the grafts were implanted below the musculoaponeurotic layer at inguinal. region of rats following the same procedure of incubation and washing. On the 8th day, the rats were examined for infection rate and their wound cultures were obtained. Results. The least amount of bacterial growth was detected in the samples obtained from gold-palladium coated grafts; whereas the highest rate of growth was found in samples of naive grafts. The superficial surgical site infection rate was 0% in gold-palladium coated, 30% in gold-coated and 100% in naive polypropylene group. The bacterial growth rate from wound cultures confirmed the superficial surgical site infection rates in all groups. Conclusion. Prosthetic graft infection with S. epidermidis can be prevented by coating the graft with gold-palladium or gold. (c) 2006 Elsevier Inc. All rights reserved

Fabrication of biomaterials via controlled protein bubble generation and manipulation.

In this work, we utilize a recently developed microbubbling process to generate controlled protein (bovine serum albumin, BSA) coated bubbles and then manipulate these to fabricate a variety of structures suitable for several generic biomedical applications, tissue engineering, and biosensor coatings. Using BSA solutions with varying concentrations (20, 25, and 30 wt %) and cross-linking (terephthaloyl chloride) mechanisms, structures were fabricated including porous thin films with variable pore sizes and thickness (partially cross-linked coupled to bubble breakdown), scaffolds with variable pore morphologies (fully cross-linked), and coated bubbles (no cross-linking), which can be used as stand-alone delivery devices and contrast agents. The movement of typical biosensor chemicals (catechol and hydrogen peroxide) across appropriate film structures was studied. The potential of formed scaffold structures for tissue engineering applications was demonstrated using mouse cell lines (L929). In addition to low cost, providing uniform structure generation and high output, the size of the bubbles can easily be controlled by adjusting simplistic processing parameters. The combination of robust processing and chemical modification to uniform macromolecule bubbles can be utilized as a competing, yet novel, tool with current technologies and processes in advancing the biomaterials and biomedical engineering remits

Evaluation of Ionotropic Cross-Linked Chitosan/Gelatin B Microspheres of Tramadol Hydrochloride

Microspheres of tramadol hydrochloride (TM) for oral delivery were prepared by complex coacervation method without the use of chemical cross-linking agents such as glutaraldehyde to avoid the toxic reactions and other undesirable effects of the chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate as cross-linking agent. Chitosan and gelatin B were used as polymer and copolymer, respectively. All the prepared microspheres were subjected to various physicochemical studies, such as drug–polymer compatibility by thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectroscopy, surface morphology by scanning electron microscopy, frequency distribution, drug entrapment efficiency, in vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). TLC and FTIR studies indicated no drug–polymer incompatibility. All the microspheres showed initial burst release followed by a fickian diffusion mechanism. DSC and XRD analysis indicated that the TM trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. From the preliminary trials, it was observed that it may be possible to formulate TM microspheres by using biodegradable natural polymers such as chitosan and gelatin B to overcome the drawbacks of TM and to increase the patient compliance

Effect of chloroquine on phagolysosomal fusion in cultured guinea pig alveolar macrophages: Implications in drug delivery

The aim of this study was to evaluate the effects of chloroquine on phagolysosomal fusion (PLF) in cultured guinea pig alveolar macrophages (AMs). This technique may be of significance for antitubercular drugs, because the survival of Mycobacterium tuberculosis is linked to evasion of PLF. Guinea pig AMs were obtained from anesthetized animals after exsanguination. The AMs were cultured at a density of 1×106 cell/mL in 24-well plates after attachment to 13-mm coverslips. Culture conditions were at 37°C, with 95% air/5% CO2 in Roswell Park Memorial Institute (RPMI) 1640 medium with 10% heat-inactivated fetal bovine serum. Rhodamine-dextran (70 kd) was incubated with the cells at 0.25 mg/mL for 24 hours to label the lysosomes. Chloroquine treatment where indicated was performed at 10–20 μ g/mL for 1 hour. Fluorescent BioParticles were then added, and PLF was monitored by formation of an organge-yellow fluorescence on fusion of green fluorescent BioParticles with rhodamine-labeled lysosomes. PLF endpoints were measured by scoring for the percentage of orange-yellow cells in the field of view. Image analysis to measure the intensity of the orange-yellow color was performed by obtaining a, b values for 5×5 pixel areas using the Photo Adobe program 4.0.1