To overcome drawbacks related to repeated opioid administration during the treatment of chronic pain, several controlled-drug delivery systems of opioids have been designed. In order to address some of the limitations of the existing systems, injectable peptide-based hydrogels represent a promising alternative. This work reports on the design and synthesis of short amphipathic peptide-based hydrogels as controlled-drug delivery systems for opioids. Based on the lead sequence H-FEFQFK-NH2, a new set of peptide hydrogelators was designed including β-homo and d-amino acids, mainly aiming at enhancing proteolytic resistance of the peptides, and which hypothetically allows an extension of the drug release period. After self-assembly in aqueous media, the resulting hydrogels were characterized by dynamic rheometry, cryogenic transmission electronic microscopy and their cytotoxicity was assessed. The cryoTEM images of drug loaded hydrogels show the association of microcrystals of the loaded drug along the axes of the fibres, suggesting that the peptide fibres play a key-role as nucleating site for the drug crystals. Hydrogelators devoid of cytotoxicity were considered for further in vivo evaluation. Upon encapsulation of morphine and 14-methoxymetopon, two opioid analgesics, the applicability of the peptide hydrogels as controlled-drug delivery platforms was validated in vivo using the mouse tail-flick test. A sustained antinociceptive effect was observed after subcutaneous injection of the drug loaded gels and, in comparison with the lead sequence H-FEFQFK-NH2, novel sequences revealed extension of the in vivo antinociception up to 72–96 h post injection. 相似文献
High-spin states of the mass A= 39 mirror pair 39K and 39Ca were investigated via the fusion-evaporation reaction 28Si +16O at 125 MeV beam energy. The Gammasphere array in conjunction with the 4π charged-particle detector array Microball and neutron detectors was used to detect γ rays in coincidence with evaporated light particles. The results of the first
high-spin study of the Tz=−1/2 nucleus 39Ca are discussed in terms of mirror symmetry and compared to spherical shell-model calculations in the 1d3/2–; 1f7/2 configuration space.
Received: 18 August 1999 相似文献
Stacks of nuclear emulsion were exposed at the Brookhaven AGS to a 10.6 GeV/n beam of gold nuclei in the BNL 868 experiment. A preliminary analysis of the main features of the interactions of these nuclei is reported here and compared with those observed previously at lower energies,E<1 GeV/n. The multiplicity and pseudo-rapidity distributions of the singly charged particles emitted both in central and in minimum bias samples of interactions have been analyzed in order to look for any non random effects indicative of the nuclear state during the interactions. The fragmentation characteristics of the gold projectiles appear to be different at 10.6 GeV/n from those at ≦1 GeV/n incident energy. Fission of the gold projectiles, which was relatively frequent at low energy, is almost entirely suppressed. Some of alpha particles from the projectile are emitted with very large transverse momenta. In gold-emulsion interactions the residual target nuclei are significantly smaller than in oxygen and sulfur interactions in emulsion.
The degree of excitation of the emulsion target nuclei due to nuclear interactions of oxygen and sulfur projectiles at 200 GeV/nucleon incident energy has been investigated. Using the plausible assumption that the numberNb of slow particles emitted from the struck target nucleus can be interpreted as a measure of the temperatureT of the residual nucleus, we have found that there exists a critical temperatureTc of the excited target nucleus. For Ag and Br target nuclei this temperature corresponds to <Nb>≌12 and it is attained when the impact parameters are less than about 4 fm. 相似文献