24 research outputs found
Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year period of biological therapy.
Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach
Keyhaneh Karimi, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka, Rita Ambrus Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary Abstract: Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 µm and displayed an enhanced aerosol performance with fine particle fraction up to 80%. Keywords: antibiotic, carrier-free formulation, quality by design, aerodynamic evaluation, dry powder for inhalatio
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Novel, cell-penetrating molecular transporters with flexible backbones and permanently charged side-chains
Various cell-penetrating peptides have been discovered recently that can translocate across plasma membranes and can even carry large cargo molecules into the cells. Because under physiological conditions most of these peptides carry considerable positive charges due to the presence of basic amino acids such as arginine, we decided to investigate whether molecular transporters composed of permanently charged side-chains also possess such cell penetrating ability. Arginine-rich oligomers that have a backbone with increased flexibility due to incorporation of non-alpha-amino acids (epsilon-aminocaproic acid) have been found to be effective molecular transporters. Here, we report the preparation of analogue structures by replacing the arginine residues with the quaternary form of a novel redox amino acid (Nys(+)) that contain a trigonelline moiety; it has already been shown possible to replace the original basic amino acid side-chain of neuropeptides without significant activity-loss due to the sufficiently close steric and electronic analogy between the new Nys(+) and the original side-chains (in their protonated form, e.g., Arg(+), Lys(+)). A nonamer analogue showed transporter activity resulting in increased cellular uptake in human carcinoma (HeLa) cells
Definition and validation of the Design Space for co-milled nasal powder containing nanosized lamotrigine
5-HT6/7 receptor antagonists facilitate dopamine release in the cochlea via a GABAergic disinhibitory mechanism
In humans, serotonin (5-HT) has been implicated in numerous physiological and pathological processes in the peripheral auditory system. Dopamine (DA), another transmitter of the lateral olivocochlear (LOC) efferents making synapses on cochlear nerve dendrites, controls auditory nerve activation and protects the sensory nerve against overactivation. Using in vitro microvolume superfusion techniques we tested 5-HT6 and 5-HT7 receptor antagonists whether they can influence dopamine (DA) release from the guinea-pig cochlea in control and in ischemic conditions using currently available and new 5-HT6 and 5-HT7 antagonists and mixed antagonists, which were synthesized and characterized for the current study. While the 5-HT7 antagonist SB-258719 was ineffective, SB-271046, which blocks the 5-HT6 receptor, caused a significant increase in cochlear DA release what is contradictory with the excitatory nature of this type of receptor. Moreover, the mixed 5-HT6/7 antagonist EGIS-12233 induced an even more pronounced increase in the resting DA release. To understand why the block of an excitatory receptor results in an increase instead of a decrease in function, we investigated the possible involvement of an indirect neural mechanism through an inhibitory system. In the presence of the GABA(A) receptor blocker bicuculline, EGIS-12233 failed to increase the release of DA, suggesting that the serotonin receptor modulation of DA release from the lateral olivocochlear efferents in the cochlea was produced indirectly by decreasing the GABAergic inhibitory tone on dopaminergic nerve endings. The mixed 5-HT7/D-4 receptor antagonist EGIS-11983 significantly increased both the stimulation-evoked and the resting DA release, while the selective D4 blocker L-741,741 alone had no significant effect. Ischemia, simulated by oxygen and glucose deprivation from the perfusion solution had no action on the effect of the drugs. Drugs that can increase the release of DA from LOC terminals in the cochlea may have a role in the treatment of sensorineural hearing loss
Synthesis and properties of novel Ba(II)Fe(III) layered double hydroxides
Double hydroxides of Ba(II) and Fe(III) were prepared by the co-precipitation method. Co-precipitation was facilitated by applying highly alkaline, carbonate free NaOH solutions with varying base concentrations (2-20 M). The substances, thus obtained, were characterised by thermal methods. XRD spectra of samples treated at various temperatures, Mossbauer and X-ray absorption spectroscopies. It was found that in extremely concentrated base solutions (>= 10 M) layered double hydroxides, most probably with intercalated OH ions, were formed, indeed, while at low base concentration the Fe(III) ions were precipitated as various oxyhydroxides and the Ba(II) ions remained dissolved. (C) 2009 Elsevier B.V. All rights reserved