60 research outputs found
Liposomal targeting of antimicrobial agents to bacterial infections
Failure of antimicrobial treatment is observed frequently in hospitalized patients resulting in
morbidity and mortality, A possible way to improve antimicrobial treatment is the targeted
delivery of antimicrobial agents, This thesis describes a study on tihe use of long-Circulating
liposomes for the targeted delivery of antimicrobial agents to sites of bacterial infections, In
this chapter an introduction is given on the use of targeted drug delivery in infectious
diseases, which is followed by the aims and outline of this thesis
In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime
Antimicrobial agents may interact synergistically. But to ensure synergy
in vivo, the drugs should both be present at the site of infection at
sufficiently high concentrations for an adequate period of time.
Coencapsulation of the drugs in a drug carrier may ensure parallel tissue
distributions. Since liposomes localize preferentially at sites of
infection, this mode of drug delivery could, in addition, increase drug
concentrations at the focus of infection. The therapeutic efficacy of
gentamicin and ceftazidime coencapsulated into liposomes was examined by
monitoring survival in a rat model of an acute unilateral pneumonia caused
by antibiotic-susceptible and antibiotic-resistant Klebsiella pneumoniae
strains. It is shown that administration of gentamicin in combination with
ceftazidime in the free form either as single dose or as 5-day treatment
resulted in an additive effect on rat survival in both models. In
contrast, targeted delivery of liposome-coencapsulated gentamicin and
ceftazidime resulted in a synergistic interaction of the antibiotics in
both models. Consequently, liposome coencapsulation of gentamicin and
ceftazidime allowed both a shorter course of treatment at lower cumulative
doses compared with administration of the antibiotics in the free form to
obtain complete survival of rats. Liposomal coencapsulation of synergistic
antibiotics may open new perspectives in the treatment of severe
infections
Ісак Мазепа: перші кроки у великій політиці
Досліджується становлення світоглядних позицій та формування політичних поглядів І. Мазепи.Исследуется становление мировоззренческих позиций и формирование политических взглядов И. Мазепы.Formation world outlook positions and formation of political views of I. Mazepa is investigated
Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation
Inflammation is an important component of various cancers and its inflammatory cells and mediators have been shown to have prognostic potential. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. In earlier studies, we demonstrated that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen-specific manner. Increased expression of FLC was observed within stroma of various human cancers including those of breast, colon, lung, pancreas, kidney and skin, and FLC expression co-localized with areas of mast cell infiltration. In a large cohort of breast cancer patients, FLC expression was shown associated with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was found expressed in areas of inflammatory infiltration and its expression was significantly associated with poor clinical outcome. Functional importance of FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC-mediated mast cell activation strongly reduced tumor growth. Collectively, this study identifies FLCs as a ligand in the pro-tumorigenic activation of mast cells. Blocking this pathway may open new avenues for the inhibition of tumor growth, while immunohistochemical staining of FLC may be helpful in the diagnosis and prognosis of cancer
Fusogenic coiled-coil peptides enhance lipid nanoparticle-mediated mRNA delivery upon intramyocardial administration
Supramolecular & Biomaterials Chemistr
Density, heterogeneity and deformability of red cells as markers of clinical severity in hereditary spherocytosis
Altres ajuts: This work was generated within the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) - FPA No. 739541Hereditary spherocytosis (HS) originates from defective anchoring of the cytoskeletal network to the transmembrane protein complexes of the red blood cell (RBC). Red cells in HS are characterized by membrane instability and reduced deformability and there is marked heterogeneity in disease severity among patients. To unravel this variability in disease severity, we analyzed blood samples from 21 HS patients with defects in ankyrin, band 3, á-spectrin or β-spectrin using red cell indices, eosin-5- maleimide binding, microscopy, the osmotic fragility test, Percoll density gradients, vesiculation and ektacytometry to assess cell membrane stability, cellular density and deformability. Reticulocyte counts, CD71 abundance, band 4.1 a:b ratio, and glycated hemoglobin were used as markers of RBC turnover. We observed that patients with moderate/severe spherocytosis have short-living erythrocytes of low density and abnormally high intercellular heterogeneity. These cells show a prominent decrease in membrane stability and deformability and, as a consequence, are quickly removed from the circulation by the spleen. In contrast, in mild spherocytosis less pronounced reduction in deformability results in prolonged RBC lifespan and, hence, cells are subject to progressive loss of membrane. RBC from patients with mild spherocytosis thus become denser before they are taken up by the spleen. Based on our findings, we conclude that RBC membrane loss, cellular heterogeneity and density are strong markers of clinical severity in spherocytosis
Liposomes in Biology and Medicine
Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS
ICS-283: a system for targeted intravenous delivery of siRNA
ICS-283 was developed within Intradigm Corporation as a system that is
designed for the systemic delivery of therapeutic small interfering (siRNA) to
sites of pathological angiogenesis. The non-viral siRNA delivery system is based
on synthetic nanoparticles, known as TargeTran™ (Intradigm Corporation),
which functions as a broad-platform technology to deliver siRNA to specific
target cells in diseased tissues. The system is constructed to incorporate different
functionalities that address critical needs for successful nucleic acid delivery.
The TargeTran synthetic vector is a self-assembling, layered nanoparticle
that protects and targets siRNA to specific cell types in pathological tissues. At
present, ICS-283 is the only antiangiogenic siRNA delivery system that is
designed for intravenous administration to treat angiogenesis-driven diseases
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