Formulation, pharmacokinetics, and antibacterial activity of florfenicol-loaded niosome.

The growing interest in employing nano-sized pharmaceutical formulations in veterinary medicine has prompted the exploration of the novel nanocarriers' ability to augment the therapeutic outcome. In this study, we harnessed niosomes, spherical nanocarriers formed through non-ionic surfactant self-assembly, to enhance the therapeutic efficacy of the broad-spectrum antibiotic florfenicol. Pre-formulation studies were conducted to identify the optimal parameters for preparing florfenicol-loaded niosomes (FLNs). These studies revealed that the formulation that consisted of Span 60, cholesterol, and dihexadecyl phosphate (DDP) at a molar ratio of 1:1:0.1 exhibited the highest entrapment efficiency (%EE) and uniform size distribution. In vitro antibacterial testing demonstrated the niosomal capacity to significantly reduce florfenicol minimum inhibitory concentration (MIC) against E. coli and S. aureus. Pharmacokinetic profiles of free florfenicol and FLN were assessed following oral administration of 30 mg florfenicol/kg body weight to healthy or E. coli-infected chickens. FLN exhibited a substantially higher maximum plasma concentration (Cmax) of florfenicol compared to free florfenicol. Furthermore, FLN showed significantly higher area under the curve (AUC0-t) than free florfenicol as revealed from the relative bioavailability studies. Lethal dose (LD) 50 values for both free florfenicol and FLN exceeded 5 g/kg of body weight, indicating high safety profile. Assessment of mortality protection in mice against lethal E. coli infections showed the significantly higher capability of FLN to improve the survival rate (75%) than free florfenicol (25%). Collectively, these findings demonstrate the niosomal ability to improve the oral bioavailability as well as the antibacterial activity of the incorporated veterinary antibiotic florfenicol.

Maca roots: A potential therapeutic in the management of metabolic disorders through the modulation of metabolic biochemical markers in rats fed high-fat high-carbohydrate diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Maca root (Lepidium meyenii Walp.) is a Peruvian plant of the Brassicaceae family. Maca roots are popular food supplements used to treat a variety of ailments described traditionally as enhancing metabolic and health conditions. AIM OF THE STUDY: Metabolic syndrome (MetS) has been the real scourge globally, affecting more than one-fourth of the global population. MetS causes the development of multi-organ illnesses, including altered blood cholesterol and sugar levels, oxidative stress, and hypertension. This study evaluated maca root total methanolic extract (MTE) as a potential nutraceutical to manage the complications of MetS. MATERIALS AND METHODS: After the first 4 weeks of a high-fat high-carbohydrate diet (HFCD), streptozotocin (STZ) was injected in Wistar rats to induce the MetS model. Animals were treated orally with MTE at 100 mg/kg and 300 mg/kg for 4 weeks compared to metformin at 200 mg/kg after confirmation of diabetes. RESULTS: One month of MTE supplementation in HFCD-fed rats remarkably decreased the elevation of blood glucose and lipids, improved liver function and insulin resistance, additionally it successfully restored the state of inflammatory and oxidative stress. The extract was standardized to contain total phenolics equal to 24.45 ± 0.96 µg Gallic acid/mg extract. CONCLUSIONS: Our findings suggest that MTE improves MetS by reducing hyperglycemia, hyperlipidemia, inflammation, and oxidative stress. While also improving beta cell secretory functions, implying that MTE could be used as a balancing drug in the prevention and treatment of metabolic abnormalities linked to type 2 diabetes.

Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride-induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions.

The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men's reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males' reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.

Effectiveness of natural biomaterials in the protection and healing of experimentally induced gastric mucosa Ulcer in rats.

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.

Evaluation of anti-Alzheimer activity of Echinacea purpurea extracts in aluminum chloride-induced neurotoxicity in rat model.

Alzheimer's disease (AD) is one of the neurodegenerative illnesses that impair individual life & increase the demand for caregivers with no available curative medication right now. Therefore, there is a growing concern about employing herbal medicine to limit AD progression & improve patients' life quality, thus potentiating its add-on therapy. In addition, herbs are cost-effective & accessible with nearly no side effects. In the same vein, our study aimed to investigate the potency of Echinacea purpurea (EP) flower extracts to ameliorate the neurodegenerative effect of Aluminum chloride (AlCl3) in a rat model. Moreover, mechanistic studies, including impact on the cholinesterase activity, redox status, inflammatory mediators, behavior performance, glucose level & histopathology, were carried on. Our results showed that 250 mg/kg of Aqueous (AQ) & Alcoholic (AL) extracts of EP inhibited cholinesterase, restored oxidative balance, down-regulated IL-6 & TNF-α cytokines & improved behavior performance in vivo that was reflected in the brain picture by decreasing neuronal degeneration & amyloid plaques in cerebral cortex & hippocampus. The potency of both extracts was compared to reference drugs & AlCl3 positive control group. The AQ extract showed greater potency against COX-1, COX-2 & α-amylase in vitro, while the AL extract was more potent against cholinesterase in vitro, inflammatory cytokines, behavior & pathological improvement in vivo. Conclusively EP overcame AlCl3-induced neurobehavioral toxicity in the rat model via different pathways, which support its regular administration to postpone progressive neural damage in AD patients.

The impact of gliadin and glutenin on the formation and structure of starch-lipid complexes.

This study evaluated the influence of the main gluten fractions (gliadin and glutenin) on the physicochemical properties of binary wheat starch-Lauric acid (WS-LA) complexes during heat processing to explore the complex structure and digestion of WS-LA in the presence of gluten. Ternary WS-LA-glutenin complexes were prepared at different pH (5.2 and 7), whereas WS-LA-gliadin was prepared using ethanol, and their physicochemical properties were analyzed. We found that the addition of glutenin displayed a sharper and higher diffraction peak than samples without protein, which increased short-range order structure (low full width at half-maximum (FWHM) of the band at 480 cm-1) and good thermal stability (melting peak appeared at a higher temperature); the opposite was shown for gliadin. Even though glutenin increased the resistant starch (RS) content than WS-LA, all samples prepared in 65% ethanol showed higher RS content than WS-LA-glutenin samples. These findings might improve our understanding of the relationship between gliadin/glutenin and binary complexes and provide a theoretical basis for preparing starch-based foods with a low glycemic index.

Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan-Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study.

Brucellosis is a common zoonotic infection, particularly in the developing world. The recommended treatment regimens for brucellosis involve the use of two medications such as doxycycline and curcumin in order to avoid relapses and prolonged use of these drugs. Doxycycline has excellent activity in the acidic phagolysosomal environment, while curcumin modulates the immune system function and macrophage activity. Due to the intracellular existence of Brucellae and the different anti-immune mechanisms of Brucella, the treatment of Brucella infection faces many limitations. The design of nanosystems is a promising treatment approach for brucellosis. The objective of this study was to design and evaluate the efficacy of in situ pH-responsive curcumin-loaded niosome hydrogel and doxycycline-loaded chitosan-sodium alginate nanoparticles as chemotherapeutic agents against brucellosis. The prepared formulae showed a spherical nano shape with a slow drug release pattern and small particle size. The prepared formulae were evaluated in vivo using Guinea pigs experimentally infected with Brucella melitensis biovar3. The prepared formula combination gave a significant high reduction rate of Brucella spleen viable count compared with that of untreated controls at p < 0.05. The results showed that the treatment schemes were not fully successful in eliminating Brucella infection in Guinea pigs; however, they significantly (p < 0.05) reduced the viable Brucella count in a shorter time and sub-therapeutic doses. Collectively the novel prepared formulae could be a successful therapy for the effective treatment of brucellosis infection at the recommended therapeutic doses. Graphical abstract.

Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-ß1.

Neuroprotective impact of transforming growth factor ß1 (TGF-ß1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-ß1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-ß1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.

In-depth hepatoprotective mechanistic study of Phyllanthus niruri: In vitro and in vivo studies and its chemical characterization.

Phyllanthus niruri L. is a widespread tropical plant which is used in Ayurvedic system for liver and kidney ailments. The present study aims at specifying the most active hepatoprotective extract of P. niruri and applying a bio-guided protocol to identify the active compounds responsible for this effect. P. niruri aerial parts were extracted separately with water, 50%, 70% and 80% ethanol. The cytoprotective activity of the extracts was evaluated against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cells. Bioassay-guided fractionation of the aqueous extract (AE) was accomplished for the isolation of the active compounds. Antioxidant activity was assessed using DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and ferric reducing antioxidant power (FRAP). The in vivo hepatoprotective activity of AE was evaluated in CCl4-induced hepatotoxicity in rats at different doses after determination of its LD50. Pretreatment of clone-9 and Hepg2 with different concentrations of AE (1, 0.1, 0.01 mg/ml) had significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) against CCl4 injures, and restored the activity of the natural antioxidants; glutathione (GSH) and superoxide dismutase (SOD) towards normalization. Fractionation of AE gave four fractions (I-IV). Fractions I, II, and IV showed a significant in vitro hepatoprotective activity. Purification of I, II and IV yielded seven compounds; corilagin C1, isocorilagin C2, brevifolin C3, quercetin C4, kaempferol rhamnoside C5, gallic acid C6, and brevifolin carboxylic acid C7. Compounds C1, C2, C5, and C7 showed the highest (p< 0.001) hepatoprotective potency, while C3, C4, and C6 exhibited a moderate (p< 0.001) activity. The AE exhibited strong antioxidant DPPH (IC50 11.6 ± 2 µg/ml) and FRAP (79.352 ± 2.88 mM Ferrous equivalents) activity. In vivo administration of AE in rats (25, 50, 100 and 200 mg/kg) caused normalization of AST, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol (TC), triglycyrides (TG), total bilirubin (TB), glucose, total proteins (TP), urea and creatinine levels which were elevated by CCl4. AE also decreased TNF-α, NF-KB, IL-6, IL-8, IL10 and COX-2 expression, and significantly antagonizes the effect of CCl4 on the antioxidant enzymes SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSP). The histopathological study also supported the hepatoprotective effect of AE. P. niruri isolates exhibited a potent hepatoprotective activity against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cell lines through reduction of lipid peroxidation and maintaining glutathione in its reduced form. This is attributable to their phenolic nature and hence antioxidative potential.

Nano-engineered delivery systems for cancer imaging and therapy: Recent advances, future direction and patent evaluation.

Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual role of early diagnosis and therapy to cancer patients. In this review, we have focused on various types of theranostic polymer and metal nanoparticles for their role in cancer therapy and imaging concerning their limitation, future application such as dendritic cell cancer vaccination, gene delivery, T-cell activation and immune modulation. Also, some of the recorded patent applications and clinical trials have been illustrated. The impact of the biological microenvironment on the biodistribution and accumulation of nanoparticles have been discussed.