9 research outputs found
Preparation and characterization of beta-glucan particles containing a payload of nanoembedded rifabutin for enhanced targeted delivery to macrophages
β-glucan particles (GP) are polymeric carbohydrates, mainly found as components of cell wall fungi, yeast, bacteria and also in cereals such as barley and oat, and have been recently shown to have application in macrophagetargeted drug delivery. The aim of this study was to prepare and characterize GP containing a large payload of Rifabutin (RB), an anti-tuberculosis drug effective against MDR-TB at lower MIC than Rifampicin. GP were prepared from yeast cells by acidic and alkaline extraction were either spray dried or lyophilized, prior to RB loading and alginate sealing. The FTIR and 13C-NMR spectra of the GP confirmed a β-(1→3) linked glucan structure, with a triple-helical conformation. The spray dried GP exhibited better characteristics in terms of uniformity, size range (2.9 to 6.1 μm) and more than 75 % particles were below 3.5 μm. The RP-HPLC analysis of spray dried GP revealed drug entrapment and drug loading up to 81.46 ± 4.9 % and ~40.5 ± 1.9 %, respectively, as compared to those dried by lyophilization. Electron microscopy showed nearly spherical and porous nature of GP, and the presence of drug ‘nanoprecipitates’ filling the pore spaces. The formulation showed adequate thermal stability for pharmaceutical application. The particles were readily phagocytosed by macrophage(s) within 5 min of exposure.
Drug release occurred in a sustained manner via diffusion, as the release kinetics best fit for drug release was obtained using Higuchi’s equation. Thus, the spray dried GP-based-formulation technology holds promise for enhanced targeted delivery of anti-TB drug(s) to macrophage within a therapeutic window for the clearance of intracellular bacteria
Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Review
ABSTRACT: Hepatotoxicity, a serious adverse drug reaction in tuberculosis (TB) patients receiving anti-TB drugs, is one of the most challenging clinical problems worldwide. Despite increasing awareness of clinicians and public, even now it remains an enormous problem and causes of hospitalization and life-threatening events. Considering the importance of anti-TB drug-induced hepatotoxicity (DIH) as a major obstacle to achieve successful treatment of TB, this review article deals with the current understanding of anti-TB-DIH, its incidence, mechanism of liver damage induced by different anti-TB drugs and various risk factors responsible for anti-TB-DIH, which might provide suitable information for future studies to develop safer treatment for TB. Further, this review article focuses on the role of oxidative stress in the pathogenesis of anti-TB-DIH. In addition, the possible involvement of genetic polymorphism of drug metabolizing enzymes with respect to anti-TB-DIH is also discussed in this review
Fieldwork in my Backyard: Experiences with Threshold Learning based on Distributed Fieldworks in Project-based Courses
Mushroom-Derived Nanoparticles in Drug Delivery Systems – Therapeutic Roles and Biological Functions
In this era of globalization, there is a need for green synthesis of nanoparticles (NPs), which should lessen the tremendous energy consumption, the utilization of toxic compounds, and time, which can help save the environment from hazardous effects. Green synthesis attempts to utilize products from natural agents like plants and fungi because of their profound availability of bio compounds. The NPs derived from them exhibit anticancer, antibacterial, antimicrobial, antioxidant, anti-diabetic, and immunomodulatory properties because of their unique physical and chemical properties. These extraordinary properties make them promising agents in medicine and agriculture areas. The review has targeted the mush-room-derived NPs and bioactive compounds, including the nutritional content of mushrooms with their multipurpose properties, followed by encapsulation and delivery of the biotherapeutics. These NPs have found significant applications in advancing industrial and biomedical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and con-trol the shape and size of NPs
Recent Advances in Nanocarrier Based Therapeutic and Diagnostic Approaches in Tuberculosis
Tuberculosis is the second most fatal infectious disease; each year, it causes millions of deaths worldwide. Although several anti-TB drugs are currently available, the problem with these drugs is that they require a prolonged duration of treatment, with high drug doses. In addition, patient non-adherence to therapy subsequently leads to the development of multidrug-resistant and ex-tensively drug-resistant tuberculosis. Therefore, we need to develop an effective and robust nano-carrier-based drug delivery system to overcome these issues and improve the therapeutic potential of drug dose/duration and patient compliance. This review article focuses on the cur-rently available various nanotechnology-based therapeutic approaches, including lipid nanopar-ticles, polymeric particles, carbon nanotubes, glucan, and alginate-based nano-carrier systems for effective anti-TB drug delivery to host macrophage for mycobacterium killing. Finally, we also present some promising recent nanotechnology-based mycobacterial detection systems us-ing silver nanoparticles, silica nanoparticles, magnetic nanoparticles, quantum dots, and magnet-ic barcode assay that have recently emerged as the latest diagnostic tool. Functionalized nano-materials for emerging Aggregation-induced photodynamic therapy as next-generation theranostics have also been discussed as a novel option for TB diagnosis and therapy
Inhalable microparticles containing isoniazid and rifabutin target macrophages and ‘stimulate the phagocyte’ to achieve high efficacy
469-474Macrophage responses to infection with Mycobacterium tuberculosis (MTB) and treatment with soluble isoniazid (INH) plus rifabutin (RFB) versus microparticles containing equivalent amounts of drugs were compared. It was investigated whether macrophages driven to alternative activation upon infection with MTB could be rescued to display the classical activation phenotype. It was established that microparticles sustain high levels of drugs in cytosol of macrophages for longer period as compared to soluble drugs. Microparticles co-localized with intracellular bacteria, and induced a variety of innate bactericidal responses, including induction of free radicals, alteration of mitochondrial membrane potential and apoptosis. The data strongly suggest that additional benefit may be derived from the nature of the drug delivery system, which fulfils Koch’s dictum ‘stimulate the phagocyte’ for curing tuberculosis