Effects of clofazimine on planktonic and biofilm growth of Mycobacterium tuberculosis and Mycobacterium smegmatis.

Mycobacteria form lipid-rich biofilms that restrict the efficacy of antimicrobial chemotherapy, possibly necessitating the use of lipophilic antibiotics. In the current study, the activity of one such agent, clofazimine, against Mycobacterium tuberculosis and Mycobacterium smegmatis planktonic cells and biofilms was investigated. Minimum inhibitory concentrations (MICs) of clofazimine were determined for planktonic cultures, whilst minimum bactericidal concentrations (MBCs) were determined for planktonic, biofilm-producing and biofilm-encased organisms using standard bacteriological procedures.

Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products.

Polyvalent immunoglobulin G (IgG) products obtained by fractionation of human plasma are used to treat a broad range of conditions, including immunodeficiency syndromes and autoimmune, inflammatory, and infectious diseases. Recent incidences of increased thromboembolic events (TEEs) associated with intravenous (IV) IgG (IVIG) led to recalls of some products and increased regulatory oversight of manufacturing processes in order to ensure that products are essentially free of procoagulant/thrombogenic plasma protein contaminants. Laboratory investigations have now identified activated factor XI (FXIa) as the likely causative agent of IVIG-related TEEs.

Inhaled microparticles containing clofazimine are efficacious in treatment of experimental tuberculosis in mice.

Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 μg/ml in vitro.

Clofazimine: current status and future prospects.

Clofazimine, a lipophilic riminophenazine antibiotic, possesses both antimycobacterial and anti-inflammatory activities. However, its efficacy has been demonstrated only in the treatment of leprosy, not in human tuberculosis, despite the fact that this agent is impressively active in vitro against multidrug-resistant strains of Mycobacterium tuberculosis. Recent insights into novel targets and mechanisms of antimicrobial and anti-inflammatory activity coupled with the acquisition of innovative drug delivery technologies have, however, rekindled interest in clofazimine as a potential therapy for multidrug- and extensively multidrug-resistant tuberculosis in particular, as well as several autoimmune diseases.

Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies.

Pulmonary delivery of substances in small animal models is often useful for experimental testing of various vaccine and drug candidates. One of the most challenging elements to such protocols is the efficient disposition of test materials in the lungs of mice. Herein we detail a means to deliver dry powders of an inhalant live-attenuated Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine against Mycobacterium tuberculosis to the lungs of mice.

Spray drying TB vaccines for pulmonary administration.

Background: New developments in materials science provide innovative technologies that allow mucosal immunization against tuberculosis. Recent studies report that spray-drying Mycobacterium bovis Bacillus Calmette-Guérin (BCG) allows efficient aerosol delivery of TB vaccines to the lung.

Objectives: To consider powder formulation of BCG for inhalation by spray-drying and its potential application to other vaccines given the unique challenges in the process, formulation and delivery.

Immunization by a bacterial aerosol.

By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization.

Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.

Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content.

Drying a tuberculosis vaccine without freezing.

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.

Dielectrophoretic manipulation of surface-bound DNA.

Dielectrophoretic manipulation enables the positioning and orientation of DNA molecules for nanometer-scale applications. However, the dependence of the dielectrophoretic force and torque on the electric field magnitude and frequency has to be well characterised to realise fully the potential of this technique. DNA in solution is attracted to the strongest electric field gradient (i.