1,721,021 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
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
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
Determinazione in campioni biologici di sonde fluorescent veicolate in strutture vescicolari non fosfolipidiche mediante HPLC-FLD e spettrofotometria
No full textDrug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting
Full text linkThe blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful
Improvement 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)
Simultaneous determination of Gemcitabine Hydrochloride and Irinotecan Hydrochloride in rat plasma by high performance liquid chromatography-diode array detector
No full textThis comunication reports a easy and quick HPLC-PDA method for the simultaneous analysis of Irinotecan Hydrochloride and Gemcitabine Hydrochloride in rat plasma samples both after single drug administration and drugs association. Gemcitabine Hydrochloride is commonly administered to treat non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, and in combination with paclitaxel for the treatment of breast cancer in the metastatic phase. Additionally Irinotecan Hydrochloride was used to treat colorectal cancer (CRC), gynecological cancers, carcinomas, non-small cell and small cell lung cancer. The drugs were detected simultaneously by using a Zorbax Extend C-18 column (250 mm × 4.6 mm; 5 m particle size) in gradient elution mode. The chromatographic analysis was performed in 15 minutes. The analytical method was calibrated and validated from 0.1 to 18 g/mL for both drugs. Rat plasma was used as biological samples during the analysis; while the 3-methylxanthine was used as internal standard. The performance of analytical method was further tested in rat plasma samples collected after single dose administration of drug or their association. Results demonstrated that HPLC-PDA method allows to detect the drugs in the range of concentrations herein reported and the analytical method is accurate and selective. The limit of quantification of the method was 0.1 g/mL. These values are similar or little higher to data published in literature, which are performed using sophisticated and expensive detectors such as mass spectrometer, and wich consider merely only one drug and not their association. The weighted-matrix matched standard curves showed a good linearity until 18 g/mL. The parallelism tests were also performed to evaluate if over-range samples can be analyzed after dilution, without affecting the performance of validated method. The intra- and inter-day precision (RSD%) values were ≤7.14% and ≤11.5%, respectively, for the full range of analysis. The intra- and inter-day trueness (Bias%) values ranged from -11.5% to 1.70% for the two drugs. At the best of our knowledge, this is the first HPLC-PDA method which allows to detect simultaneously Irinotecan Hydrochloride and Gemcitabine Hydrochloride in rat plasma, both after single and drugs association administration in order to evaluate how can interact and modify the pharmacokinetic parameter
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
Nanostructured Lipid Carriers (NLC) for the topical delivery of lutein
No full textLutein is a natural carotenoid with antioxidant properties, already proven in various topical applications. A 20% suspension of lutein in safflower oil (FloraGLO®Lutein) represents a good raw material for the production of creams and other semisolid formulations. However, the high viscosity of FloraGLO® and poor chemical stability of lutein in the suspension represents a practical limitation to its use. An efficient method was proposed in this study for taking benefit of the liquid oily composition of FloraGLO®, by realizing a nanostructured carrier system (NLC) able to ensure a controlled release of lutein and improve its permeability across the skin. NLC were prepared with different percentages of FloraGLO® as the liquid phase of NLC. The physical stability of NLC was assessed by storage at room conditions and by Turbiscan accelerated analysis. All the produced nanocarriers were perfectly tolerated after application on the skin. In an in vivo model of UV-induced skin erythema, the lutein-loaded NLC were able to improve the photo-protective effects of the antioxidant compared to the commercial suspension, when the NLC formulations were applied before inducing the erythema. This study also proved for the first time the possibility of converting a liquid formulation into a solid, modified release nanocarrier with more manageable formulative features
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