Effectiveness of sugammadex for cerebral ischemia/reperfusion injury

AbstractCerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis

A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations

WOS: 000310850300001PubMed ID: 23180964Aim: To develop a suitable buccal bioadhesive gel formulation containing cyclosporine A solid lipid nanoparticles (CsA SLNs) for the treatment of recurrent aphthous stomatitis. Methods: The suitability of the prepared formulations for buccal application was assessed by means of rheological studies, textural profile analysis, and ex vivo drug-release studies. Plastic flows, typical gel-like spectra, and suitable mechanical properties were obtained from prepared formulations. The retention time was explored in in vivo distribution studies and the effect of the gel containing CsA SLNs on the healing of oral mucosal ulceration was investigated in an animal model. In vivo distribution studies are a very important indicator of the retention time of formulations at the application site. Results: Distribution studies showed that 64.76% +/- 8.35% of the formulation coded "F8+SLN" remained on the buccal mucosa 6 hours after application. For the second part of the in vivo experiments, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without the active agent; the second group with the gel formulation containing CsA SLNs; and the third group, used as the control group, received no treatment. Wound healing was established by scoring of the rate of wound healing on Days 3, 6, 9, and 12. Histological observations were made on the same days as the scoring studies. The bioadhesive gel formulation that included CsA SLNs increased the rate of mucosal repair significantly. Conclusion: This study has shown that the bioadhesive gel formulation containing CsA SLNs reported here is a promising candidate for the topical treatment of recurrent aphthous stomatitis.Research Foundation of Ege UniversityEge University [09/ECZ/026]; Novartis Drug CompanyThe authors wish to thank the Research Foundation of Ege University (09/ECZ/026) and the Novartis Drug Company for financial support given to this study

The Effects of α

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats

Age-related changes in apoptosis in rat hippocampus induced by oxidative stress

Also known as programmed cell death, apoptosis is a sequence of events that leads to elimination of cells without releasing harmful substances into the surrounding area. Apoptosis may be induced by intracellular or extracellular signals. Certain apoptotic signals activate mitochondrial proapoptotic events and increase reactive oxygen species (ROS). Increased ROS production may lead to oxidative stress. The goal of our study was to characterize age-related changes in apoptosis induced by oxidative stress in the hippocampus. Rats 2, 7, 21 and 38 days old, and adult rats were used for our study. Hippocampal CA1, CA2, CA3 and dentate gyrus apoptosis, and hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels were measured. We found that numbers of hippocampal neurons were low in rats 2, 7 and 21 days old (CA1, p < 0.001; CA3, p < 0.05; gyrus dentatus, p < 0.001). The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cell count was highest in the CA1 and dentate gyrus of 21-day-old rats. Among 21-day-old rats, the hippocampal TBARS levels and SOD enzyme activity were high, whereas GPx activity was low. These results demonstrate that the hippocampal CA1 and dentate gyrus of 21-day-old rats are more prone to damage by oxidative stress

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

WOS: 000387891800001PubMed ID: 27358561This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT (R) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.Ege UniversityEge University [12/ECZ/010]This study was supported by a research grant from Ege University (12/ECZ/010). We would like to acknowledge Ege University Pharmaceutical Sciences Research Center (FABAL) for enabling us to use its laboratory instruments (Nuve Stability Cabin)

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations

WOS: 000382949300002PubMed ID: 25259424Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (similar to 13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.Scientific and Technological Research Council of Turkey-TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S433]This work was supported by The Scientific and Technological Research Council of Turkey-TUBITAK (Project number: 109S433)