Search results for "Oral administration"
showing 10 items of 165 documents
Lipid Nanoparticles as Potential Gene Therapeutic Delivery Systems for Oral Administration.
2017
Background Gene therapy has experimented an increasing attention in the last decades, due to its enormous potential applications in the medical field. It can be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides) to treat or prevent a disease state, generally a geneticbased one. Application Other applications, like treating viral, bacterial or parasite infections or development of vaccines are gaining also interest. Efficient gene therapy is mainly dependent on the ability of the highly labile genetic material to reach the therapeutic target. For this purpose, different delivery systems have been designed and extensively investigated. Nanoparticles offer a broad ran…
Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model
2017
The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. …
Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.
2019
Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we…
Odiparcil, a potential glycosaminoglycans clearance therapy in mucopolysaccharidosis VI—Evidence from in vitro and in vivo models
2020
International audience; Mucopolysaccharidoses are a class of lysosomal storage diseases, characterized by enzymatic deficiency in the degradation of specific glycosaminoglycans (GAG). Pathological accumulation of excess GAG leads to multiple clinical symptoms with systemic character, most severely affecting bones, muscles and connective tissues. Current therapies include periodic intravenous infusion of supplementary recombinant enzyme (Enzyme Replacement Therapy-ERT) or bone marrow transplantation. However, ERT has limited efficacy due to poor penetration in some organs and tissues. Here, we investigated the potential of the β-D-xyloside derivative odiparcil as an oral GAG clearance therap…
The metabolism of mono-(2-ethylhexyl) phthalate (MEHP) and liver peroxisome proliferation in the hamster.
1988
This study has investigated the in vivo metabolism of mono-(2-ethylhexyl) phthalate (MEHP), the initial metabolite of di-(2-ethylhexyl) phthalate in mammals, and the hepatic peroxisome proliferation induced by this compound following multiple oral administration to hamsters. Hamsters received [14C]-MEHP, by gavage, at doses of 50 and 500 mg/kg body wt on each of three consecutive days. Urine was collected every 24 hours and metabolite profiles were determined using capillary gas-chromatography. Multiple high doses of MEHP (500 mg/kg) induced a change in the relative proportions of metabolites produced. As previously reported for the rat, metabolites derived from sequential ω-following by β…
Signature of Circulating Biomarkers in Recurrent Non-Infectious Anterior Uveitis. Immunomodulatory Effects of DHA-Triglyceride. A Pilot Study
2021
The purpose of this study was to identify circulating biomarkers of recurrent non-infectious anterior uveitis (NIAU), and to address the anti-inflammatory effects of triglyceride containing docosahexaenoic acid (DHA-TG). A prospective multicenter study was conducted in 72 participants distributed into: patients diagnosed with recurrent NIAU in the quiescence stage (uveitis group (UG)
Milk and blood biomarkers associated to the clinical efficacy of a probiotic for the treatment of infectious mastitis
2016
Previous studies have shown the efficacy of oral administration of selected lactobacilli strains to treat mastitis. The objective of this study was to find microbiological, biochemical and/or immunological biomarkers of the probiotic effect. Women with (n=23) and without (n=8) symptoms of mastitis received three daily doses (109 cfu) of Lactobacillus salivarius PS2 for 21 days. Samples of milk, blood and urine were collected before and after the probiotic intervention, and screened for a wide spectrum of microbiological, biochemical and immunological parameters. In the mastitis group, L. salivarius PS2 intake led to a reduction in milk bacterial counts, milk and blood leukocyte counts and i…
Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing muc…
2017
Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylac…
Localized Interleukin-12 for Cancer Immunotherapy
2020
Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest…
Chiral Serum Pharmacokinetics of 4-Fluoroamphetamine after Controlled Oral Administration
2021
Abstract Over the last two decades, misuse of 4-fluoroamphetamine (4-FA) became an emerging issue in many European countries. Stimulating effects last for 4–6 hours and can impact psychomotor performance. The metabolism of amphetamine-type stimulants is stereoselective and quantification of (R)- and (S)-enantiomers has been suggested for assessing time of use. To date, no data on enantioselective pharmacokinetics is available for 4-FA in serum samples. An enantioselective liquid chromatography−tandem mass spectrometry (LC–MS-MS) method was developed using a chiral Phenomenex® Lux 3 μm AMP column. Validation of the method showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL…