1,721,015 research outputs found
Peptide derivatives as agonists or antagonists of formylpeptide receptors: analysis of their effects on neutrophils
No full textThe effects of peptide derivatives as agonists or antagonists of formylpeptide receptors are described, taking into account the related cellular responses by neutrophils. These effects are related to the structure of peptide derivatives, some of which are potent anti HIV-1 agents. Finally, formylpeptide receptor models are depicted
Solid lipid microparticles for the stability enhancement of the polar drug N6-cyclopentyladenosine
No full textThe objective of this study was to prepare solid lipid microparticles (SLMs) loaded with the polar adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA). The microparticles were produced by the conventional hot emulsion technique, using different lipidic carriers (tristearin, glyceryl behenate and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The controlled release of CPA was achieved only with stearic acid microparticles. This phenomenon has been attributed to direct acid-base interactions between the basic nitrogen atoms of CPA and stearic acid. These SLMs were characterized by release studies, scanning electron microscopy and powder X-ray diffraction analyses.
The obtained particles showed proper features in terms of morphology and size distribution (3.2-10.3 microm), with a drug loading of 0.15±0.04%.
The influence of the SLMs carrier system on CPA stability was investigated in vitro using human whole blood. The degradation kinetic of microparticle-entrapped CPA was significantly lower from that measured for the free CPA. The overall results indicate that it was possible to achieve the encapsulation and controlled release of a polar drug, such as CPA, within a lipid matrix without resorting to the complex methods generally used for the preparation of these systems
New formulation strategies of nanoparticles for the controlled relase of drugs with small or large molecuar weight
No full textWe report a study of encapsulation and release from polymeric micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA). Classical preparation methods of the particles (nanoprecipitation, single or double emulsion/solvent evaporation) are compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. CPA-loaded nanoparticles obtained by classical methods drastically reduce their drug content and the ability to control its release. The novel method allows us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a control of the drug release. Any drastic reduction of BSA particle content is observed by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induces only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method are similar: the micro- and nano-spheres prepared by double emulsion technique show an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase; the release from micro- and nano-particles obtained by the novel method is complete and quite regular, being characterized by a little burst release followed by a fast phase. The results can be related to the strong BSA distribution in the surface or in the core of microparticles (observed by confocal laser scanning microscope) obtained by the classical or novel methods, respectively
Polymeric nanoparticles as drug controlled release systems: a new formulation strategy for drugs with small or large molecular weight
No full textWe report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel
method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control
of the drug release with respect to CPA-loaded microparticles. The novel preparation method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained
for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induced
only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively
Materie Prime: Eccipienti
No full textLe forme farmaceutiche per la somministrazione dei farmaci contengono sostanze ausiliarie note come eccipienti, che svolgono un ruolo importante nei processi di fabbricazione, conservazione e liberazione del principio attivo
Caratterizzazione di potenziali profarmaci di derivati adenosinici ad attività antiischemica.
No full textVitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation
No full textDiclofenac (Diclo), its ascorbic acid (AA) or 6-amino-AA (AA-NH2) pro-drugs (AA-Diclo or AA-NH-Diclo) were prepared
and evaluated on human retinal pigment epithelium (HRPE) cells to investigate their ability to interact with the vitamin C
transporterSVCT2and their cellular uptake. Furthermore, stabilities in physiological fluids of these compounds were investigated.For kinetic experiments, AA-Diclo was incubated in Tris-HCl buffer, human plasma or whole blood. The extracted samples were analysed by HPLC. AA-Diclo was hydrolysed following first order kinetics in buffer, plasma (t1/2 about 10 h) and whole blood (t1/2 about 3.5 h). Transport and inhibition assays were performed by adding [14C]AA and the above-mentioned unlabelled compounds to plated HRPEcells. Intracellular accumulationwas measured incubatingHRPEcells with increasing concentrations of unlabelled compounds, following by HPLC analysis. Diclo resulted as a non-competitive inhibitor of AA-transport, showing a Na+-dependent and ascorbate-independent uptake. AA-Diclo behaved as a competitive inhibitor, but it was not transported into cells, whereas its analogue AA-NH-Diclo showed a decreased inhibitory activity. Stability studies suggest AA-Diclo as a potential candidate to enhance the Diclo short half life in vivo. The discovery of a Na+-dependent transporter for Diclo on HRPE cells opens new perspectives for targeting diclofenac into the brain
Phe-D-Leu-Phe-D-Leu-Phe derivatives as formylpeptide receptor antagonists in human neutrophils: cellular and conformational aspects
No full textWe synthesized several Phe-D-Leu-Phe-D-Leu-Phe analogues in which tert-butyloxycarbonyl and four different ureido
substituents were included at the N-terminal of the peptides, obtained as free acid and methyl-ester derivatives. Their
biological action was analysed on human neutrophil responses induced by N-formyl-Met-Leu-Phe (fMLF). Several in vitro
assays were carried out: receptor binding, measurement of Ca2+ intracellular concentration, chemotaxis, superoxide anion
production and enzyme release. A conformational investigation, using infrared absorption and circular dichroism, was also
performed. Our results demonstrate that the compounds examined prefer an ordered conformation (L-turn) in amphipathic
environment, and are able to antagonize the neutrophil functions evoked by fMLF. Moreover, the extent of inhibition of
Ca2+ intracellular enhancement, as well as of superoxide anion production and granule enzyme release, appears related to
their affinity toward the formylpeptide receptor. The free acid peptide derivatives appear to be more active antagonists than
the methyl-ester ones. ß 1999 Elsevier Science B.V. All rights reserved
- …
