We aimed to investigate the effects of two nitric oxide donors in acute inflammation in rats. The experiment was carried out on white Wistar rats, randomly distributed in 4 groups of 5 animals each; the substances were administered intraperitoneally as follows: Group 1 (SS): saline solution 0.1mL/100 g body weight (control); Group 2 (IND): indometacin 150 mg/kg body weight; Group 3 (NEB): nebivolol 1 mg/kg body weight; Group 4 (GSNO): S-nitroso-glutathione 1 mg/kg body weight. An experimental model of acute hind paw inflammation with carrageenan was used for the researches. The influence of the nitric oxide donors on blood parameters, specific inflammatory and immune markers was evaluated 24 h, respectively 72 hours after the injection of irritant agent. The experimental protocol was implemented according to the recommendations of our University Committee for Research and Ethical Issues. The administration of nitric oxide donors nebivolol and S-nitroso-glutathione was accompanied by a substantial diminution of paw edema, as well as by an important decrease in the percent of lymphocytes, a reduction of interleukin 6 and tumor necrosis factor alpha values. The effects of nebivolol were more accentuated than of S-nitroso-glutathione, but less intense than of indomethacin in the experiment. The treatment with nebivolol and S-nitroso-glutathione produced anti-inflammatory effects on local acute inflammation in the carrageenan-induced paw edema test in rats.
Background and Objectives In the past few decades, the studies concerning the natural polysaccharide chitosan have been centered on a new direction: its hepatoprotective action. The aim of our study was to evaluate the influence of previously designed chitosan lipid vesicles on the liver damage induced by alcohol consumption in mice. Materials and Methods The study involved the oral administration of substances in one daily dose as follows: Group 1 (control): water; Group 2 (control alcohol): 5% alcohol in water; Group 3 (CHIT): 0.1 mL/10 g body weight chitosan solution in animals treated with alcohol; Group 4 (CHIT-ves): 0.1 mL/10 g body chitosan vesicles in animals treated with alcohol; Group 5 (AcA): 200 mg/kg body ascorbic acid in animals treated with alcohol. In order to evaluate liver damage after alcohol consumption, the following hematological parameters were tested: the activity of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase; serum values of urea and creatinine; the phagocytic capacity of polymorphonuclear neutrophilsin peripheral blood;serum opsonic capacity;bactericidal capacity of peritoneal macrophages; and the activity of malondialdehyde, glutathione peroxidase, superoxide dismutase and lactate dehydrogenase. Results and Conclusion The treatment with chitosan vesicles decreased liver enzyme activity and reduced the oxidative stress disturbances in alcoholic mice, thus repairing the hepatic functional and structural damages. These beneficial activities of chitosan vesicles were comparable with ascorbic acid effects in alcoholic mice.
Nanoantibiotics have proved improved pharmacokinetic characteristics and antimicrobial features. Recent studies have shown non-toxicity, non-immunogenicity, antioxidant, anti-hyperlipidemic, and hepatocyte protective actions, among other advantages of chitosan-based nanoparticles. The purpose of our study was the structural analysis of novel chitosan-coated vesicles entrapping erythromycin (ERT) and the assessment of their biocompatibility in mice. According to the group in which they were randomly assigned, the mice were treated orally with one of the following: distilled water; chitosan; ERT; chitosan vesicles containing ERT. Original nanosystems entrapping ERT in liposomes stabilized with chitosan were designed. Their oral administration did not produce sizeable modifications in the percentages of the leukocyte formula elements, of some blood constants useful for evaluating the hepatic and renal function, respectively, and of some markers of oxidative stress and immune system activity, which suggests a good biocompatibility in mice. The histological examination did not reveal significant alterations of liver and kidney architecture in mice treated with chitosan liposomes entrapping ERT. The results indicate the designed liposomes are a promising approach to overcome disadvantages of conventional ERT treatments and to amplify their benefits and can be further studied as carrier systems.
In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the 'codrug' complex, which do not affect the release of the bioactive compounds.
Pregabalin is an anticonvulsant and analgesic drug that stirs more and more the interest of the researchers. Its stability, solubility and taste can be modified by obtaining complexes with cyclodextrins. For this purpose, in the present study betacyclodextrin and hydroxypropyl-betacyclodextrin were included. The obtaining of inclusion complexes was confirmed by ATR-FTIR spectroscopy and UV spectroscopy. The results demonstrated that it is possible to develop inclusion complexes of pregabalin with betacyclodextrin and hydroxypropyl-betacyclodextrin, with moderate efficiency.
Depression [major depressive disorder (MDD)] is a mood disturbance of multifactorial origin, associated with high rates of morbidity and mortality, lack of work productivity, adverse health behaviors, and increased healthcare expenses. MDD is a leading cause of suicide, and it affects the prognosis of chronic conditions (heart diseases, diabetes, and cancer, among others). Current pharmacological treatment for MDD covers different classes of drugs, including tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants. The aim of this chapter is to review the literature, highlight the side effects of newer antidepressants, and especially point out the most important aspects of the latest agents approved for the treatment of MDD in adults: desvenlafaxine, levomilnacipran, vilazodone, and vortioxetine. Desvenlafaxine is a SNRI and the primary active metabolite of venlafaxine; also a SNRI, levomilnacipran is an enantiomer of the racemate milnacipran. Vilazodone and vortioxetine are multimodal antidepressants, which combine SSRI activity with additional receptor activity. Although they have proven efficacy in treating MDD and are being investigated for other possible indications, further detailed clinical trials are needed to establish their pharmacotoxicological profile, following prolonged administration in patients who may suffer from various comorbidities.
Microparticles made from naturally occurring biopolymers, such as chitosan, appear to be promising carrier systems for the sustained release of orally administered drugs. In the current study, we followed a microencapsulation technique based on the spray-drying method to prepare metoprolol tartrate-containing chitosan microparticles with various compositions. The prepared microparticulate drug delivery systems were investigated for their morphological, structural, and thermal behavior by optical microscopy, infrared spectroscopy, and thermogravimetric analysis. Microencapsulation efficiency and drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastric fluid (SGF) (pH 1.2) and simulated intestinal fluid (SIF) (pH 6.8) revealed that the drug-to-polymer ratio is an important element in controlling the release features of microparticulate systems based on CHT. Also, the pH of the dissolution fluid plays an important role in the release of the drug substance from the microspheres. Additionally, the analysis of the release kinetic mechanism concluded that in SGF media as well as in SIF media, the MT from the chitosan-based microparticles is released by means of a Fickian diffusion process.
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