1,721,008 research outputs found
Sistemi vescicolari formati da bilayer asimmetrici a struttura doppia per la veicolazione di materiale genetico.
No full textLa presente invenzione è relativa a sistemi liposomiali per la veicolazione di materiale genetico identificati con il seguente acronimo (AVs). Gli AVs presentano una struttura costituita da due bilayer asimmetrici formati da: i) un bilayer interno caricato positivamente per la presenza di fosfolipidi cationici, in grado di formare complessi elettrostatici con il materiale genetico; ii) un bilayer esterno neutro o caricato negativamente e formato sia da fosfolipidi in grado di fondersi attraverso le membrane biologiche, che da polimeri idrofilici e/o amfipatici coniugati ai fosfolipidi, in grado di migliorare la stabilità e le proprietà biofarmaceutiche del sistema sopramolecolare.
L’invenzione descrive, inoltre, una nuova metodica per realizzare gli AVs, partendo da due bilayer asimmetrici preparati separatamente utilizzando la metodica d’evaporazione del solvente con formazione del film fosfolipidico (TLE) e la successiva formazione di due formulazioni liposomiali auto-assemblate per ottenere gli AVs
Physicochemical characterization of non ionic surfactant vesicles forming innovative supramolecular nanocarriers
No full textα-Acylamino-β-lactone N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors Encapsulated in PLGA Nanoparticles: Improvement of the Physical Stability and Protection of Human Cells from Hydrogen Peroxide-Induced Oxidative Stress
Full text linkN-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that preferentially catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide, which has been shown to exhibit neuroprotective and antinociceptive properties by engaging peroxisome proliferator-activated receptor-α. A few potent NAAA inhibitors have been developed, including α-acylamino-β-lactone derivatives, which are very strong and effective, but they have limited chemical and plasmatic stability, compromising their use as systemic agents. In the present study, as an example of a molecule belonging to the chemical class of N-(2-oxo-3-oxetanyl)amide NAAA inhibitors, URB866 was entrapped in poly(lactic-co-glycolic acid) nanoparticles in order to increase its physical stability. The data show a monomodal pattern and a significant time- and temperature-dependent stability of the molecule-loaded nanoparticles, which also demonstrated a greater ability to effectively retain the compound. The nanoparticles improved the photostability of URB866 with respect to that of the free molecule and displayed a better antioxidant profile on various cell lines at the molecule concentration of 25 μM. Overall, these results prove that the use of polymeric nanoparticles could be a useful strategy for overcoming the instability of α-acylamino-β-lactone NAAA inhibitors, allowing the maintenance of their characteristics and activity for a longer time
LIPOSOMAL SYSTEM WITH KILLER TNF-APOPTOSIS INDUCED LIGAND (KILLERTRAIL), PRO-APOPTOTIC-DIRECTING
No full textThe present invention relates to the development of transport systems of the liposomal type which have PEGylated compounds conjugated with derivatives of the family of Tumor Necrosis Factor cytokines on the surface of the vesicular structure. The conjugation strategy is to bind the protein, preferably TRAIL, more preferably KillerTRAIL, in monomeric form, to the polyethylene glycol (PEG) via a thiol group (-SH) of the polypeptide chain
Supramolecular devices to improve the treatment of brain diseases
No full textThe blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such as having structures made up of biocompatible and biodegradable materials, the possibility of bypassing the BBB in a non-invasive manner (without structural modifications) and the possibility of being structurally modified to modulate the biopharmaceutical properties of the encapsulated compounds. Polymolecular (liposomes, niosomes, nanogels) and oligomolecular (cyclodextrins) devices have potential clinical applications in brain drug delivery, being capable of active targeting that can concentrate bioactives in the brain
Post-insertion parameters of PEG-derivatives in phosphocholine-liposomes
No full textThe insertion of specific derivatives into pre-formed colloidal systems has been shown to be a useful method for modifying their pharmacokinetic characteristics and biodistribution profiles. In this experimental work the effect of the post-insertion of different PEG-derivatives into pre-formed 100-nm liposomes made up of various lipid mixtures (DMPC, DPPC, DOPC, DSPC and cholesterol at different molar ratios) was investigated. The vesicles were incubated with increasing amounts of DSPE-mPEG2000 as sterically stabilized micelles (5, 10 and 15% w/w with respect to the liposomal lipid mixture) in order to favour the insertion of the PEG-lipid into the liposomal bilayer. The colloidal formulations were characterized by photo-correlation spectroscopy; the DSPE-mPEG2000 integrated into the pre-formed liposomes was demonstrated by means of field flow fractionation while the amount of post-inserted compound was quantified using a suitable spectrophotometric assay (I2 assay). Similar investigations have been performed using PEG-derivatives characterized by a different molecular weight. The physico-chemical properties of the various liposomal formulations were influenced by the post-insertion of PEG-derivatives. The lipid mixture made up of saturated phospholipids and cholesterol proved to be the best, post-insertion (P.I.E.). The post-insertion technique may be a suitable approach to be used in personalized (nano)medicine
Determinazione in campioni biologici di sonde fluorescent veicolate in strutture vescicolari non fosfolipidiche mediante HPLC-FLD e spettrofotometria
No full textImprovement of the therapeutic treatment of inflammatory bowel diseases following rectal administration of mesalazine-loaded chitosan microparticles vs Asamax®
No full textThe development of innovative strategies for the efficacious treatment of inflammatory bowel diseases (IBD) still remains a goal for pharmaceutical research. Targeting the lower section of the intestine is the main aim of therapy because it is the compartment primarily affected by IBDs. Mesalazine was microencapsulated in chitosan particles in order to modulate its unfavorable pharmacokinetic profile exploiting the bioadhesive feature of the polysaccharide and increase the anti-inflammatory effect of the drug following its rectal administration in an in vivo model of induced IBD. The chitosan microparticles (1-4 μm mean size) allowed efficient retention of the mesalazine and a prolonged drug release lasting up to 48 h. In vitro and in vivo experiments confirmed the significant mucoadhesion feature of the formulation by means of mucin assay and CLSM experiments and demonstrated its therapeutic efficacy at a drug concentration 2-fold lower than the commercial formulation Asamax® (13 mg/kg vs 26 mg/kg)
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