Intranasal In Situ Gel of Apixaban-Loaded Nanoethosomes: Preparation, Optimization, and In Vivo Evaluation.

The present study was conducted to formulate ethosomal thermoreversible in situ gel of apixaban, an anticoagulant drug, for nasal delivery. Ethosomes were formed, of lecithin, cholesterol, and ethanol, by using thin-film hydration method. The prepared ethosomes were characterized by Zetasizer, transmission electron microscope, entrapment efficiency, and in vitro study. The selected ethosomal formula (API-ETHO2) was incorporated in gel using P407 and P188 as thermoreversible agents and carbopol 934 as mucoadhesive agent. Box-Behnken design was used to study the effect of independent variables (concentration of P407, P188, and carbopol 934) on gelation temperature, mucoadhesive strength, and in vitro cumulative percent drug released at 12h (response variables). The optimized formulation was subjected to compatibility study, ex vivo permeation, histopathological examination for the nasal mucosa, and in vivo study. API-ETHO2 was spherical with an average size of 145.1±12.3 nm, zeta potential of -20±4 mV, entrapment efficiency of 67.11%±3.26, and in vitro % release of 79.54%±4.1. All gel formulations exhibited an acceptable pH and drug content. The optimum gel offered 32.3°C, 1226.3 dyne/cm2, and 53.50% for gelation temperature, mucoadhesive strength, and in vitro percent released, respectively. Apixaban ethosomal in situ gel evolved higher ex vivo permeation (1.499±0.11 µg/cm2h) through the nasal mucosa than pure apixaban gel. Histopathological study assured that there is no necrosis or tearing of the nasal mucosa happened by ethosomal gel. The pharmacokinetic parameters in rabbit plasma showed that intranasal administration of optimized API-ethosomal in situ gel achieved higher Cmax and AUC0-∞ than unprocessed API nasal gel, nasal suspension, and oral suspension. The ethosomal thermoreversible nasal gel established its potential to improve nasal permeation and prolong anticoagulant effect of apixaban.

Effects of dietary white mulberry leaves on hemato-biochemical alterations, immunosuppression and oxidative stress induced by Aeromonas hydrophila in Oreochromis niloticus.

The present work was designed to assess the potential hemato-biochemical protective action, immunemodulatory and antioxidant conclusions of varied concentration of white mulberry Morus alba leaves (MAL) extract supplementation on Nile tilapia (Oreochromis .niloticus). A total two hundred and forty of O. niloticus were haphazardly sorted into four groups. The control (CT) group was fed on basal diet. A group MAL1, MAL3 and MAL5 was fed on 1, 3 and 5 g/kg MAL respectively for thirty days. On day thirty one, half of replicates in each group were challenged by 0.5 ml × 108Aeromonas hydrophila where, the residual replicates were kept without challenge. A. hydrophila challenged tilapias revealed anemia that alleviated by supplementation with 5 g/kg MAL also, recovers the shift of leucogram prompted by the challenge. Elevation of alkaline phosphatase, aminotransferases, lactate dehydrogenase and malondialdehyde (ALP, ALT, AST, LDH and MDA) in CT, MAL1 and MAL3 in the challenged replicates respectively where within normal at MAL5. Supplementation with MAL5 showed more potent antioxidant and immune reaction than MAL1 and MAL3. There were a rapid increase of immunoglobulin M, lysozymes, nitric oxide, catalase and superoxide dismutase and their allied genes expression (IgM, CAT and SOD) in MAL groups with contrast in CT challenged groups. Where in challenged groups, there was suppression in genes expression of interleukins (8 and 1 beta) and interferon ɤ (IL8. IL-1ß and INFɤ). Tilapias challenged by A. hydrophila unveiled plentiful surge in the percentage of mortality in CT challenged fish (80%), followed by the groups supplemented with MAL1 and MAL3 were (73.33%) where MAL5 was 20%. The mortalities have been halted from the 6th, 13th, 14th and 15th days in, MAL5, MAL3, MAL1, and CT correspondingly. These previous results could be fulfilled that using of MAL 5 g/kg protect tilapias from hemato-biochemical alterations and enhance its immune feedback, antioxidant defense and resistance against A. hydrophila.

Effect of Chlorella vulgaris enriched diet on growth performance, hemato-immunological responses, antioxidant and transcriptomics profile disorders caused by deltamethrin toxicity in Nile tilapia (Oreochromis niloticus).

The toxic effect of deltamethrin (DM) was documented in aquaculture. There is no obtainable data on the effect of Chlorella vulgaris against DM toxicity. The current study focused on the effect of dietary supplementation with C. vulgaris (CV) on growth performance, innate immune response, antioxidant activities, and transcriptomics disorders induced by sub-lethal dose of DM in Oreochromis niloticus. A total number of 216 O. niloticus divided into four groups with tri-replicates. The 1st control group (CT) fed a basal diet, the second group fed diet enriched with 5% CV. The third group was exposed to DM (15 µg/L), where the last group fed CV and simultaneously exposed to DM as previous-mentioned. The procedure of CV feeding and DM exposure were continued for two months. Exposures to DM revealed in stunting of the growth parameters and lessening of survival ratio of tilapias with a significant decline of the erythrogram (macrocytic hypochromic anemic picture), and leucocytes immune cells and related parameters (immunoglobulin M, lysozyme) and sever shifting in the antioxidant indicators. Sever raise was monitored in hepatic and kidney markers. Also, genes expression related to immune and antioxidant parameters were severely impacted. Where tilapias received CV showed a significant increase in the growth and immune parameters besides to an improvement of hematological, antioxidant values and their related genes expressions. The fourth group that received CV simultaneous with DM exposure showed a soothing of the previous indicators and markers toward the values of tilapias fed on basal diet (CT). In turn, CV supplementation may be presented a protective effect alongside DM toxicity in O. niloticus appeared through soothing of the immune, antioxidant and related genes expressions in addition to its hepato-renal protective effects. Therefore, the current study recommended that an incorporating of 5% CV for tilapias diet could improve their growth performance, immunity, antioxidant and transcriptomics disorders induced by deltamethrin.

Efficacy of dietary Nano-selenium on growth, immune response, antioxidant, transcriptomic profile and resistance of Nile tilapia, Oreochromis niloticus against Streptococcus iniae infection.

As recently applicable, there are few studies on the impact of using nano-selenium (nano-Se) on varied fish species. Where nothing reachable focused on its impact on tilapias so, the present analysis evaluated the efficacy of using nano-Se in tilapias on immune response, antioxidant defense compared by conventional Se form. 480 O. niloticus fingerlings were haphazardly grouped firstly into three groups with four replicates of each. The control one (CT) was fed on a basal diet. The second and third one supplemented with 0.7 mg/kg-1 Se and nano-Se respectively for ten weeks. At the start day of the ninth week, two replicates from each group were injected by Streptococcus iniae where, the remaining replicates stand without challenge. Enhancement of growth performance measurements were noted in nano-Se compared to Se or CT groups. Existed anemia in S. iniae tilapias became alleviated by using nano-Se that also, improves the alteration of leucogram induced by challenge. Elevation of aminotransferases, alkaline phosphatase, lactate dehydrogenase (ALT, AST, ALP and LDH) and creatinine in Se and CT challenged replicates that seemed nearly normal by using nano-Se. Usage of nano-Se showed more powerful antioxidant activities than Se. There were an expansion of immunoglobulin M, lysozymes, glutathione peroxidase, nitric oxide, superoxide dismutase and catalase (IgM, LYZ, GPx, NO, SOD, CAT) and their related gene expression in nano-Se with contrast in Se or CT challenged groups. Nile tilapias challenged by S. iniae disclosed substantial expansion in the percentage of mortality in CT challenged fish (93.33%), followed by the group supplemented with Se (73.33%), whereas the lowermost one at fish supplemented by nano-Se (26.66%). The mortalities have been stopped from the 5th, 12th and 14th days in, nano-Se, Se and CT respectively. It can be concluded that using of Se 0.7 mg/kg-1induce immunosuppressive, antioxidant, liver and kidneys negative impact on tilapias where the same dose from nano-Se was more potent immunomodulating and antioxidant. Also it is attend in counteracting the serious impact induced by S. iniae challenge.