1,721,102 research outputs found
Investigation of Signaling in Primary Populations of Human Senescent T Cells
Mitogen-activated protein kinases, a family of three stress-related kinases, the Erks and Jnks and p38s, are activated by three-layer transphosphorylation cascades and are important for the activation, differentiation, and effector functions of lymphocytes. Recent studies on the aged immune systems from both humans and mice have uncovered a different mode of MAPK signaling that is independent of canonical activation cascades and instead occurs through simultaneous self-phosphorylation reactions within the sestrin-MAPK activation complex (sMAC), an immune-inhibitory complex not previously observed. In this chapter, we discuss methodologies to study these pathways at the population and single cell level, which allows rejuvenating immune cell differentiation and fate
Ricerche archeologiche dell'Università di Padova in Grecia. Le campagne di indagine 2001 e 2002 del teatro del Pythion di Gortina (Creta),
Il contributo illustra i risultati delle campagne di indagine archeologica condotte presso il Teatro del Pythion di Gortina a Cret
Il self-help nelle condizioni depressive: analisi dell esperienza di un gruppo di mutuo-aiuto per pazienti depressi in remissione parziale.
LIPOSOMAL APPROACH TO PHARMACEUTICS
Efficient and safe drug delivery has always been a challenge in therapy and diagnostics. The use of nanotechnology, as well as the development of nanocarriers for drug delivery, received great attention according to the evidence that they can theoretically act as “magic bullets” capable to hit the target cells while sparing normal tissues and organs. Liposomes are suitable as carriers of both hydrophilic and lipophilic drugs and are able to deliver drugs to the target site.
The vesicle properties are specifically dictated by size, shape, and surface chemistry which are able to modify the intrinsic pharmacokinetics of the drug and, eventually, the drug targeting to the pathological areas.
Liposomes can be developed in different approach to pharmaceutics. According to this, in our laboratory, liposomes have been proposed as biomembrane model in order to study the interaction between surfactant vesicles and liposomes, since it is very difficult to directly observe the membrane fusion due to the complexity of biomembranes and the high speed of the process (1). Furthermore our research involves the “classic” use of liposomes as drug delivery systems. For example they have been studied to obtain an efficient brain delivery of prodrugs to enhance the extracellular levels of L-Dopa and Dopamine in rat striatum of freely moving rat (2). Maleic and fumaric diamides of (O,O-diacetyl)- L-Dopa-methylester, synthesized in order to attenuate marked fluctuations of L-Dopa plasma levels and to overcome the problem of low bioavailability of L-Dopa, have been entrapped in liposomal formulations to obtain chemical stability in aqueous buffer solutions, slow release of LD in human plasma and sustained delivery of Dopamine in rat striatal dialysate (3). With the aim to provide a protection against chemical degradation and enzymatic metabolism and, consequently, to get a high prodrug quantity able to cross the Blood Brain Barrier, liposomal formulations of 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DOPH) were prepared and characterized (4). Polysaccharide-coated liposomes have been proposed as carrier of peptide drug by the oral route because they are able to minimize the disruptive influences on peptide drugs of gastrointestinal fluids. In particular, a modified polysaccharide, O-palmitoylscleroglucan (PSCG), was synthesized and used to coat unilamellar liposomes for oral delivery of Leuprolide, a synthetic superpotent agonist of luteinizing hormone releasing hormone receptor (5). In collaboration with the Centre for Surgical Technologies at the Faculty of Medicine of the Katholieke Universiteit of Leuven (Belgium), thermosensitive liposomes have been prepared to deliver the Cytotoxic Necrotizing Factor 1 (CNF-1) toward lung tissues, with an effective approach against the Congenital Diaphragmatic Hernia (CDH). These carriers are able to release drugs/proteins due to the hyperthermia, as a consequence of lung tissues inflammation. The preliminary studies have shown the safety of these structures in foetal rats and rabbits with CDH. Finally, in our laboratory, the phospholipidic shell was used to prepare novel nanobbubles, NBs (6) - ). These structures can act as theranostic agents. The preclinical experiments, developed in collaboration with the Queens Medical Research Institute at the University of Edinburgh, were carried out to demonstrate that ultrasound-mediated NBs destruction has the potential to open the BBB tight junctions and trigger therapeutic agent deposition in the brain. The results are very promising and suggest the possible use of NBs in the theranostic fields
Ricerche archeologiche dell'Università di Padova in Grecia. La campagna di indagine 2003 al teatro del Pythion di Gortina (Creta)
Il contributo illustra i risultati delle indagini archeologiche condotte presso il Teatro del Pythion di Gortina nell'anno 200
DLS Characterization of Non-Ionic Surfactant Vesicles for Potential Nose to Brain Application
The aim of this paper is the preparation and characterization of drug delivery systems for a potential brain delivery
by intranasal administration. It is possible to reach the central nervous system with alternative routes through which therapeutic
agents can bypass the blood brain barrier: that is the nasal administration. Intranasal drug administration is non-invasive and it
could be a promising drug delivery method for patients who suffer from chronic and crippling Central Nervous System diseases.
Among the formulation strategies for enhanced nose to brain drug delivery, the use of colloidal carriers has became a
revolutionary approach. The success of a therapeutic strategy by using nanocarriers depends on their ability to entrap drugs, to
penetrate through anatomical barriers, to efficiently release the incorporated drugs, to show a good stability in nanometric size
range and good biocompatibility. The use of vesicular systems (niosomes), in nose to brain delivery is here presented. One of the
major problems associated with nasal administration is the rapid removal of drugs or drug delivery systems, from the deposition
site through mucociliary clearance. This effect is responsible of reduction of contact time between drug or drug delivery systems
and nasal epithelium. This problem could be solved by coating nanocarriers with a mucoadhesive agent: chitosan. In this paper
the preparation and characterization of hybrid niosomes by Tween 20 and Tween 21 together with dicetyl phosphate or Span 20
and the cationic polyelectrolyte chitosan are described in order to obtain intranasal drug delivery systems. In particular through
dynamic light scattering, laser Doppler electrophoresis and fluorescence measurements the aggregation behavior between
vesicles and polyelectrolyte can be monitored. Overall phenomenology is well described in terms of the re-entrant condensation
and charge inversion behavior, observed in different colloidal systems. The physical stability of hybrid niosomes obtained by the
three different surfactants was also evaluated
Nanomedicines and nanocarriers in clinical trials: surfing through regulatory requirements and physico-chemical critical quality attributes
Elucidation of physical-chemical characteristics of investigational medicinal products should be established with suitable methodology. Characterization of nanomedicines and nanocarriers in clinical trials may require the definition of additional specific properties depending on the nature of the nanostructures or nanomaterials composing the investigational medicinal product. The availability of regulatory requirements and guidelines is investigated focusing on critical quality attributes for nanomedicines and nanocarriers, mapping them in a clinical trial setting. Current regulatory challenges and issues are highlighted. The increasing complexity of nanostructures, the innovative connotation of applied nanotechnology, and the lack in capillarity or misalignment of relevant guidelines and terminology may lead to a potential not standardized approach in the characterization of nanomedicines and nanocarriers in clinical trials and delays in the approval process. Further efforts and a proactive approach from a regulatory standpoint would be desirable to surf the wave of innovation that impact nanomedicines and nanocarriers in clinical trials, in order to support clinical drug development capitalizing on technological advances and still ensuring a strong regulatory framework. GRAPHICAL ABSTRACT: [Image: see text
Non-ionic surfactant vesicles for ammonium glycyrrhizinate delivery: in vitro characterization and in vivo evaluation on mice oedema
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