Can an Alginate-based Wound Dressing Modified with Garden Cress Substitute for COE-PAK as a Wound Dressing? An In Vitro Study.

AIM: The aim of the current study was to prepare a natural oral wound dressing from alginate modified with garden cress (GC), a rich source of antibacterial phytochemical compounds essential for wound healing. MATERIALS AND METHODS: Sodium alginate (SA) dressing (negative control group), was prepared and modified with GC seeds extracts (25 µg/mL and 50 µg/mL) as the intervention groups, and COE-PAK was the positive control group. Cytotoxicity was measured using WST-1 assay (n = 15) after 24 and 48 hours. The in vitro wound healing assay (n = 15) was assessed in terms of wound width, and cell migration rate (0, 24, 48, and 72 hours). Agar diffusion test was performed to investigate the antibacterial action (n = 15) of the groups against Streptococcus mutans and Lactobacillus casei strains. Results were significant at p ≤ 0.05. RESULTS: There was no statistically significant difference in cytotoxicity in all groups (p = 0.24 at 24 hours and 0.1 at 48 hours). Garden cress-containing groups revealed the lowest mean value of wound width (0.27 mm ± 0.01 and 0.23 mm ± 0.01 for 25 µg/mL and 50 µg/mL, respectively at 48 hours) and the highest mean value of cell migration rate (0.013 mm/hour ± 0.004 and 0.014 mm/hour ± 0.004 for 25 µg/mL and 50 µg/mL, respectively at 48 hours), in addition to the highest antibacterial action (1.49 mm ± 0.05 and 2.14 mm ± 0.09 for 25 µg/mL and 50 µg/mL, respectively against S. mutans, 1.43 mm ± 0.07 and 2.55 mm ± 0.09 for 25 µg/mL and 50 µg/mL, respectively against L. casei). CONCLUSION: Alginate wound dressing modified with GC extract could be considered a promising wound dressing material in terms of wound healing and antibacterial action. CLINICAL SIGNIFICANCE: Ready-to-use alginate-based wound dressing modified with GC extract may represent a promising natural alternative to the most commonly used oral wound dressing (COE-PAK).

Novel grape seed extract nanoparticles attenuate amikacin-induced nephrotoxicity in rats.

Amikacin (AMK), an antibiotic, is prescribed for treating various bacterial diseases like urinary tract infections, encephalitis, asthma and joint infections. The most significant side effects, which affect 1 to 10% of consumers, are kidney injury and ototoxicity. Several studies discussed the role of grape seed extract (GSE) in renoprotection against AMK. The current study aimed to extract Muscat of Alexandria grape seeds followed by its characterization to determine its bioactive components and elements. GSE nanoparticles was prepared and tested, in vitro, to determine its safety for the in vivo experiment. Experimental groups were control group I, AMK group II, GSE (50 mg/kg)-AMK group III, GSE (100 mg/kg)-AMK group IV, GSE NPs (25 mg/kg)-AMK group V and GSE NPs (50 mg/kg)-AMK group VI. Groups 2-6 received 100 mg/kg/day of AMK by intramuscular injection for two weeks for the induction of experimental nephrotoxicity. Groups 3-6 received daily doses of GSE or GSE NPs by oral gavage, concurrently, with AMK for two weeks. GSE was rich in polyphenol compounds like proanthocyanidins, phenolic acids like gallic and egallic acids, catechine and epicatechine. GSE NPs have a smooth surface and a size that ranged from 40 to 70 nm; and have an anti-oxidant, anti-inflammatory, anti-cytotoxic and anti-microbial in vitro effects. It reduced oxidative stress and inflammation that followed AMK administration; and attenuated the AMK-induced nephrotoxicity. GSE NPs were safe to be used in vivo as a renoprotective agent against AMK; where, it reduced the oxidative stress and inflammation.

Remodeled tumor immune microenvironment (TIME) parade via natural killer cells reprogramming in breast cancer.

Breast cancer (BC) is the main cause of cancer-related mortality among women globally. Despite substantial advances in the identification and management of primary tumors, traditional therapies including surgery, chemotherapy, and radiation cannot completely eliminate the danger of relapse and metastatic illness. Metastasis is controlled by microenvironmental and systemic mechanisms, including immunosurveillance. This led to the evolvement of immunotherapies that has gained much attention in the recent years for cancer treatment directed to the innate immune system. The long forgotten innate immune cells known as natural killer (NK) cells have emerged as novel targets for more effective therapeutics for BC. Normally, NK cells has the capacity to identify and eradicate tumor cells either directly or by releasing cytotoxic granules, chemokines and proinflammatory cytokines. Yet, NK cells are exposed to inhibitory signals by cancer cells, which causes them to become dysfunctional in the immunosuppressive tumor microenvironment (TME) in BC, supporting tumor escape and spread. Potential mechanisms of NK cell dysfunction in BC metastasis have been recently identified. Understanding these immunologic pathways driving BC metastasis will lead to improvements in the current immunotherapeutic strategies. In the current review, we highlight how BC evades immunosurveillance by rendering NK cells dysfunctional and we shed the light on novel NK cell- directed therapies.

Characterization of sex-related differences in allergen house dust mite-challenged airway inflammation, in two different strains of mice.

Biological sex impacts disease prevalence, severity and response to therapy in asthma, however preclinical studies often use only one sex in murine models. Here, we detail sex-related differences in immune responses using a house dust mite (HDM)-challenge model of acute airway inflammation, in adult mice of two different strains (BALB/c and C57BL/6NJ). Female and male mice were challenged (intranasally) with HDM extract (~ 25 µg) for 2 weeks (N = 10 per group). Increase in serum HDM-specific IgE showed a female bias, which was statistically significant in BALB/c mice. We compared naïve and HDM-challenged mice to define immune responses in the lungs by assessing leukocyte accumulation in the bronchoalveolar lavage fluid (BALF), and profiling the abundance of 29 different cytokines in BALF and lung tissue lysates. Our results demonstrate specific sex-related and strain-dependent differences in airway inflammation. For example, HDM-driven accumulation of neutrophils, eosinophils and macrophages were significantly higher in females compared to males, in BALB/c mice. In contrast, HDM-mediated eosinophil accumulation was higher in males compared to females, in C57BL/6NJ mice. Differences in lung cytokine profiles indicated that HDM drives a T-helper (Th)17-biased response with higher IL-17 levels in female BALB/c mice compared to males, whereas female C57BL/6NJ mice elicit a mixed Th1/Th2-skewed response. Male mice of both strains showed higher levels of specific Th2-skewed cytokines, such as IL-21, IL-25 and IL-9, in response to HDM. Overall, this study details sex dimorphism in HDM-mediated airway inflammation in mice, which will be a valuable resource for preclinical studies in allergic airway inflammation and asthma.

Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs.

Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans, in response to inhaled allergens. Female and male BALB/c mice (7-8 weeks) were intranasally challenged with the allergen house dust mite (HDM) for 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected 24 hour after the last HDM challenge from allergen-naïve and HDM-challenged mice (N=10 per group, each sex). In a human study, adult participants were exposed to nebulized (2 min) allergens (based on individual sensitivity), BALF was obtained after 24 hour (N=5 each female and male). The BALF samples were examined in immunoblots for the abundance of 10 proteins shown to increase in response to allergen in both murine and human BALF, selected from proteomics studies. We showed significant sex-bias in allergen-driven increase in five out of the 10 selected proteins. Of these, increase in eosinophil peroxidase (EPX) was significantly higher in females compared to males, in both mice and human BALF. We also showed specific sex-related differences between murine and human samples. For example, allergen-driven increase in S100A8 and S100A9 was significantly higher in BALF of females compared to males in mice, but significantly higher in males compared to females in humans. Overall, this study provides sex-specific protein biomarkers that are enhanced in response to allergen in murine and human lungs, informing and motivating translational research in allergic asthma.

Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation.

Cationic host defense peptides (CHDP) are immunomodulatory molecules that control infections and contribute to immune homeostasis. CHDP such as cathelicidin and calprotectin expression is altered in the arthritic synovium, and in the lungs of asthma and COPD patients. Recent studies suggest a link between airway inflammation and the immunopathology of arthritis. Therefore, in this study we compared the abundance of mouse cathelicidin (CRAMP), defensins, and calprotectin subunits (S100A8 and S100A9) in murine models of collagen-induced arthritis (CIA) and allergen house dust mite (HDM)-challenged airway inflammation. CRAMP, S100A8, and S100A9 abundance were significantly elevated in the joint tissues of CIA mice, whereas these were decreased in the lung tissues of HDM-challenged mice, compared to naïve. We further compared the effects of administration of two different synthetic immunomodulatory peptides, IG-19 and IDR-1002, on cathelicidin and calprotectin abundance in the two models. Administration of IG-19, which controls disease progression and inflammation in CIA mice, significantly decreased CRAMP, S100A8, and S100A9 levels to baseline in the joints of the CIA mice, which correlated with the decrease in cellular influx in the joints. However, administration of IDR-1002, which suppresses HDM-induced airway inflammation, did not prevent the decrease in the levels of cathelicidin and calprotectin in the lungs of HDM-challenged mice. Cathelicidin and calprotectin levels did not correlate with leukocyte accumulation in the lungs of the HDM-challenged mice. Results of this study suggest that endogenous cathelicidin and calprotectin abundance are disparately altered, and may be differentially regulated, within local tissues in airway inflammation compared to arthritis.

Loss of ß-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation.

Pancreatic ß-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in ß-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4-NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine ß cell maturation and identity. Mice with ß cell-specific Cnot3 deletion (Cnot3ßKO) exhibit impaired glucose tolerance, decreased ß cell mass, and they gradually develop diabetes. Cnot3ßKO islets display decreased expression of key regulators of ß cell maturation and function. Moreover, they show an increase of progenitor cell markers, ß cell-disallowed genes, and genes relevant to altered ß cell function. Cnot3ßKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for ß cell identity.

Development of folic acid-loaded nanostructured lipid carriers for topical delivery: preparation, characterisation and ex vivo investigation.

The present work is designed to achieve efficient localised skin delivery of folic acid (FA)-loaded nanostructured lipid carriers (NLCs) to infer efficient treatment of skin photoageing conditions induced via excessive exposure to ultraviolet (UV) radiation. FA NLCs were prepared by high-speed homogenisation followed by ultrasonication. The obtained NLCs revealed high encapsulation efficiencies (89.42-99.26%) with nanometric particle sizes (27.06-85.36 nm) of monodisperse distribution (PDI = 0.137-0.442), zeta potential values >|27| mV, pseudoplastic rheological behaviour, good spreadability (2.25-3.30 cm) and promoted occlusive properties throughout 48 h. Optimised NLC formulations appeared as sphere-shaped particles using transmission electron microscopy, showed improved photostability of FA and prolonged in vitro release profile best fitted to Higuchi diffusion model. Ex vivo permeation and deposition of FA, employing Wistar rat skins, depicted enhanced permeability and existence of FA in skin layers after 6 h. Based on the obtained results, FA-loaded NLC formulations demonstrate a promising modality for anti-photoageing therapy.

Essential functions of the CNOT7/8 catalytic subunits of the CCR4-NOT complex in mRNA regulation and cell viability.

Shortening of mRNA poly(A) tails (deadenylation) to trigger their decay is mediated mainly by the CCR4-NOT deadenylase complex. While four catalytic subunits (CNOT6, 6L 7, and 8) have been identified in the mammalian CCR4-NOT complex, their individual biological roles are not fully understood. In this study, we addressed the contribution of CNOT7/8 to viability of primary mouse embryonic fibroblasts (MEFs). We found that MEFs lacking CNOT7/8 expression [Cnot7/8-double knockout (dKO) MEFs] undergo cell death, whereas MEFs lacking CNOT6/6L expression (Cnot6/6l-dKO MEFs) remain viable. Co-immunoprecipitation analyses showed that CNOT6/6L are also absent from the CCR4-NOT complex in Cnot7/8-dKO MEFs. In contrast, either CNOT7 or CNOT8 still interacts with other subunits in the CCR4-NOT complex in Cnot6/6l-dKO MEFs. Exogenous expression of a CNOT7 mutant lacking catalytic activity in Cnot7/8-dKO MEFs cannot recover cell viability, even though CNOT6/6L exists to some extent in the CCR4-NOT complex, confirming that CNOT7/8 is essential for viability. Bulk poly(A) tail analysis revealed that mRNAs with longer poly(A) tails are more numerous in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Consistent with elongated poly(A) tails, more mRNAs are upregulated and stabilized in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Importantly, Cnot6/6l-dKO mice are viable and grow normally to adulthood. Taken together, the CNOT7/8 catalytic subunits are essential for deadenylation, which is necessary to maintain cell viability, whereas CNOT6/6L are not.

How tenofovir disoproxil fumarate can impact on solubility and dissolution rate of efavirenz?

Efavirenz (EFZ) and tenofovir disoproxil fumarate (TDF) can be used simultaneously in the treatment of human immunodeficiency virus type1 infection. In this work the impact of TDF, a hydrophilic drug, on the solubility and dissolution rate of EFZ, a poorly water-soluble drug, was evaluated. EFZ/TDF binary mixtures in different molar ratios were prepared. Differential scanning calorimetry (DSC) results indicate the formation of a eutectic mixture, the molar ratio of 65/35 being the eutectic point. It was observed an increase in the EFZ solubility in water and acidic conditions (0.1 N HCl and biorelevant medium), in the presence of TDF. On the other hand, there was a decreasing on EFZ solubility in phosphate buffer pH 6.8, probably influenced by the lower solubility of TDF in this medium. The high solubility of TDF in water and acidic medium may have contributed to improve the solubility of EFZ, as well as the formation of a eutectic mixture, supported by X-ray powder diffraction (XRPD) and Fourier Transform infrared spectroscopy (FTIR) analyses. However, TDF solubility and dissolution rate was not significantly influenced by the presence of EFZ.

Transdermal fennel essential oil nanoemulsions with promising hepatic dysfunction healing effect: in vitro and in vivo study.

Fennel (Foeniculum vulgare Mill.) is a member of family Apiaceae. Trans-anethole, the major component of Fennel essential oil (FEO), possesses antioxidant and hepatoprotective effects. Transdermal nanoemulsions (NEs) are advanced colloidal systems for systemic and controlled drug delivery through the stratum corneum barrier. FEO NEs were prepared using the oil Lauroglycol™ 90, as it provides a larger NE existence zone than Captex® 300, in the constructed phase diagrams. Six systems were prepared using Tween20/propylene glycol (S/CoS) in the ratios 2:1 and 3:1 with oil to S/CoS mass ratios 1:9, 2:8 and 3:7. Physicochemical characterization revealed optimum properties regarding thermodynamic stability, droplet size and pH with a Newtonian flow pattern. In vitro permeation study in rat skin revealed the highest cumulative amount permeated (µg/cm2), flux and permeability coefficient values for F4 made up of 2% FEO, 4.67% Lauroglycol™ 90, 60% S/CoS in the ratio 3:1. Results of the in vivo hepatic dysfunction study in rats indicate promising significant amelioration of liver function reflected in ALT, AST, ALP, bilirubin, albumin, malondialdehyde and ammonia plasma levels. The results signify the promising approach of FEO NEs in achieving remedy of liver toxicity. The most promising effect is inherent to F4 which imparts a more positive effect than FEO.

Application of liquisolid technology for promoting the renoprotective efficacy of walnut extracts in chronic renal failure rat model.

Chronic renal failure (CRF) is among the major health problems that could lead to increased morbidity and mortality among population. 'Nutraceuticals' is an emerging field for natural agents from plant foods that could reduce the progression of such disease. Many newly developed drugs are having bioavailability problems owing to their water insolubility. Liquisolid technique is one of the promising technological approaches to increase solubility and hence, drug absorption. The aim of the present research is to prepare and evaluate the renoprotective effect of the walnut extracts liquisolid formulations in CRF rat model. Saturation solubility study claimed PEG 400 and Tween 20 as good solubilizers for walnut extracts, thus chosen for preparation. The angle of slide was determined for the carrier; microcrystalline cellulose and coating material; silicon dioxide and liquid load factor was evaluated. Eight liquisolid systems were prepared employing 25% and 50% of liquid medication. Their flow and compressibility parameters showed good properties. Dissolution study was more in favor of formulations prepared using PEG 400. Of these, formulation F8 comprising carrier/coat ratio (10:1) and 50% liquid medication, showing superior dissolution properties was selected to perform stability and in-vivo evaluations. Two CRF induced rat groups received F8 at two oral doses (50 and 100 mg/kg). Biochemical and nutritional parameters were compared with both normal and CRF control rats. Results showed improvement of renal function, oxidative stress, antioxidant and inflammatory biomarkers as well as increased appetite and body weight gain on administration of both doses of walnut liquisolid formulation, F8.

Chitosan based Pickering emulsion as a promising approach for topical application of rutin in a solubilized form intended for wound healing: In vitro and in vivo study.

The aim of the present study is to formulate the hydrophobic drug rutin in a solubilized form, intended for wound healing, via its loading into a novel Pickering emulsion stabilized by self aggregated chitosan particles (SACP). Rutin-loaded Pickering emulsion formulae were prepared using a high speed homogenizer. They were characterized by drop test, optical microscopy, droplet size and zeta potential determination. The results revealed that SACP have a nano size and a contact angle of 42.47±1.19° that tend to stabilize O/W emulsion. The droplet size of all investigated formulations ranged between 5.8±1.1 and 18.7±3.4µm. The long term stability study revealed that formulae containing 20% and 30% oily phase were stable against coalescence, the droplet size was slightly increased with zeta potential ranged from -48.1±4.7 to -78.4±4.1mV, during the storage period up to 5 months, indicating good stability. The release of rutin was almost 100% within 24h. Treatment of the wounded skin tissue of the Albino rats with the selected formula, for ten days, revealed almost complete healing. Biochemical analysis for oxidative stress markers, hyaluronic acid and collagen type I in addition to histopathological study were performed. The results suggested that the sustained release of rutin in a solubilized form as well as the synergistic effect of other components of the prepared Pickering emulsion could have a potential wound healing effect.

Different modalities for treatment of recurrent aphthous stomatitis. A Randomized clinical trial.

BACKGROUND: The underlying etiology of recurrent aphthous stomatitis (RAS) is unclear and treatment aims to provide symptomatic and faster relief. This study compared the efficacy of diode laser, a herbal combination of Acacia nilotica and Licorice (A and L) and Amlexanox in the management of RAS. MATERIAL AND METHODS: Sixty patients with minor aphthae were selected and randomly divided into four groups of 15 each. Group I and II received adhesive preparations of a herbal mixture of A and L and a 2 mg Amlexanox paste respectively, group III received diode laser and the fourth group (control) used a placebo. Ulcer size, pain score were recorded on days 1, 2 and 5. RESULTS: Laser group showed the statistically highest mean percentage (%) of reduction in pain scores and ulcer size than the other groups. The mean % of reduction in pain scores was 43.3+20.0 at day 2 and 67.8+21.5 % at day 5 in the laser group while Amlexanox group demonstrated a 29.8 +11.3 and 61.9+24.5 mean % of reduction in pain scores at day 2 and 5 respectively. A and L group showed a lower mean % of reduction in pain scores than laser and Amlexanox groups with a 22.2+10.5 and 43.4+15.8 mean % reduction in pain scores at day 2 and day 5 respectively. Similarly the highest mean % of reduction in ulcer size was seen in the laser group being 52.7+19.8 at day 2 and 85.1+22.0 at day 5, while it was 48.1+16.5 at day 2 and 77.8+28.7 at day 5 in the Amlexanox group and 42.0+11.5 at day 2 and 63.0+20.5 at day 5 in the A and L group. CONCLUSIONS: All treatment modalities reduced pain and ulcer size than placebo group. Laser therapy demonstrated the highest percentage of reduction of pain score and ulcer size. Key words:Aphthous stomatitis, laser, herbal plants, Acacia nilotica, Licorice.

Rutin nanostructured lipid cosmeceutical preparation with sun protective potential.

Skin cancer is related to unprotected exposure to sunlight. Despite the broad expansion of sunscreen market, various researches are focused on the inefficiency and danger of sun products. This study was focused on the development of photoprotective nanoparticulate dermal preparations of the antioxidant flavonoid Rutin (RT). Nanostructured lipid carriers (NLCs) were prepared using different types of lipids. Based on particle size (PS), size distribution (PDI) and Zeta potential (Z) as well as rheological properties, NLC containing Plurol® stearique (NLC-P) and Apifil® (NLC-A) were selected and loaded with different concentrations of RT to form the medicated nanocreams. F4 (NLC-A with 2% RT) attained highest occlusive effect, drug encapsulation and release efficiencies as well as sun protective factor (SPF). Different concentrations of TiO2 were added to F4 aiming to ameliorate the sun protective effect. F7 (containing 5% TiO2) attained the highest SPF and area under the UV absorbance curve and had a critical wavelength above 370 nm, which proved its high efficiency as sunscreen. The in-vitro antioxidant effect of F7 was more than two fold that of the standard antioxidant. This study provides a suitable cosmeceutical lipidic colloidal system of Rutin to be employed as a successful photoprotective preparation.

Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-ß-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

CONTEXT: Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. OBJECTIVE: Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. MATERIALS AND METHODS: Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. RESULTS: Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. DISCUSSION: Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. CONCLUSION: Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.

Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.

CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East. OBJECTIVE: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy. MATERIALS AND METHODS: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-ß-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity. RESULTS AND DISCUSSION: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam. CONCLUSIONS: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.

The serine protease granzyme B as an inflammatory marker, in relation to the insulin receptor cleavage in human obesity and type 2 diabetes mellitus.

Chronic inflammation and insulin resistance form hallmarks of type 2 diabetes mellitus (T2DM). An increased circulating level of the serine protease granzyme B (GzmB) is observed during prolonged inflammation and is implicated in the pathogenesis of several chronic inflammatory diseases. Moreover, insulin receptor cleavage by unknown proteases, yielding elevated levels of insulin receptor α-subunit (IRα), was observed in T2DM and was proposed as a new mechanism of insulin resistance. Therefore, a possible association between GzmB and IRα is suggested. Accordingly, this study was set to explore whether GzmB and IRα levels are altered in T2DM patients with the impact of obesity. Furthermore, we aimed to identify if GzmB contributes towards inflammation and insulin resistance through its suggested extracellular activities. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition, fasting plasma insulin, GzmB, interleukin-1ß (IL-1ß), and IRα levels were estimated by enzyme linked immunosorbent assay. Levels of GzmB and IRα were found to be significantly elevated in T2DM patients compared to nondiabetic subjects. In addition, GzmB levels were positively correlated with measures of obesity and insulin resistance, IL-1ß, IRα, and other metabolic parameters. While multiple linear regression analysis revealed that both T2DM and central obesity were predicting factors for GzmB, our findings reveal a possible role of GzmB in T2DM.

Transdermal microemulsions of Glycyrrhiza glabra L.: characterization, stability and evaluation of antioxidant potential.

The purpose of the present study is to formulate Glycyrrhiza glabra root and rhizome aqueous ethanolic extract in microemulsion carrier systems intended for transdermal delivery of incorporated antioxidant actives, flavonoids and polyphenols. The results obtained reveal that the microemulsion system ME3 possesses optimum properties regarding drug content (flavonoids and polyphenols), viscosity, pH, particle size and polydispersity index, zeta potential, stability, permeation of actives and hence possesses high in vitro and ex vivo antioxidant efficacy. These results indicate also that this microemulsion shows approximately 13-fold higher ex vivo antioxidant capacity compared with the liquorice extract solution. In addition, the proposed microemulsion is simple to dispense, cost effective and provides high patient compliance and convenience because of simple topical application and avoidance of non-comfortable oral or parenteral administration.