Highest Ee Research Articles

Physical properties and stability of quercetin loaded niosomes: Stabilizing effects of phytosterol and polyethylene glycol in orange juice model

In this research, the quercetin loaded niosomes were prepared using span 60 and tween 80 surfactants by thin layer hydration–homogenization–sonication method. Phytosterol and polyethylene glycol 400 were used as stabilizers at four different concentrations. Physicochemical properties of the quercetin loaded niosomes, such as particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), antioxidant property, physical and encapsulation stability (ES%) were analyzed. Vesicle sizes varied from 86 to 149 nm with encapsulation efficiency of 61.49–95.68%. The nano-niosome formulation containing 7.14% (w/w) phytosterol/surfactant and 1% (v/w) PEG400/surfactant were selected as the optimum formulation based on having the smallest size, less PDI and the highest EE%. The obtained optimum formulations were used to fortifying orange juice model. The formulation stabilized with phytosterol showed higher ES% over 30 days storage period and after pasteurization heating. • Quercetin was encapsulated into niosome using span 60 and tween 80. • Niosomes remained in small size (<200 nm) after 30 days. • FTIR analysis confirmed interaction of quercetin with niosome by hydrogen bonds. • Encapsulation stability was significantly higher in neutral medium. • Quercetin niosomes showed medium encapsulation stability in orange juice model.

Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis

ObjectiveThe present work was aimed to develop gefitinib solid lipid nanoparticles (GFT-SLN) using novel lipids (Lipoid S PC-3) and to analyse its cell cytotoxicity and tissue distribution efficacy. MethodsGFT SLNs were prepared by a modified hot homogenization method using a variable concentration of lipid (Lipoid S PC-3) and poloxamer 407. GFT SLNs were characterised for physicochemical properties, in vitro drug release, cell cytotoxicity (MCF-7 cell lines), in vivo tissue distribution studies and stability analysis. ResultsThe mean particle size of SLNs was between 178 ± 10 to 348 ± 15 nm. A higher EE (>92%) and negative zeta potential (mV) was observed in all SLNs. FTIR and DSC data exhibit no possible interaction between the drug and excipients. PXRD reveal the amorphous nature of SLNs. SEM images show SLNs were of nanosize (<178.73 ± 10.66 nm) and spherical in shape. The in vitro release of SLNs showed an initial burst release (25%) within 2 h followed by a sustained release (>90%) during 72 h. Kinetic analysis of GFT SLNs fits best to the Higuchi model (R2 = 0.935). In vitro cytotoxicity of SLN demonstrated higher antitumour activity (cell viability >65%) in comparison to free drug (p < 0.05). In vivo tissue distribution studies show higher drug concentration in the liver (28,930 ± 91 ng), followed by kidneys (22,284 ± 1626 ng) and less in the brain (7042 ± 62 ng) (p < 0.05). GFT SLN was stable at 40 ± 2 °C/75 ± 5% RH and refrigerated temperature (4 ± 2 °C) during 3 months. ConclusionGFT SLNs developed using novel lipoid S PC-3 lipid offer higher antitumour efficacy and better drug distribution in tissues.

Synthesis and physicochemical characterization of rhamnolipid-stabilized carvacrol-loaded zein nanoparticles for antimicrobial application supported by molecular docking

Carvacrol is a phenolic monoterpenoid obtained from the genera of Origanum, Thymus, Satureja, and Lippia. It is a hydrophobic phytoconstituent that readily tends to decay while processing leading to restricting its potential application. In the current study, zein/rhamnolipid (ZRL of 306 nm) complex nanoparticles were loaded with carvacrol successfully (CRZRL of 271 nm) to explore its antimicrobial activity and obtained the MIC value of 135 μg/ml and 270 μg/ml against P. syringae (bacterial canker) and F. oxysporum (Fusarium wilt) respectively. These complex nanoparticles were further characterized by DLS, FE-SEM, DSC, FT-IR, H1NMR, docking, and HPLC studies. The strong interaction of carvacrol with zein and rhamnolipid complex nanoparticles which showed characteristic peaks in FTIR as well as H1NMR were also supported by our docking studies. This strong interaction resulted in higher EE (95%) as well as LE (42%), confirmed by HPLC studies. Docking studies further revealed the presence of stronger Π-Π interaction within binding and active sites of zein through which rhamnolipid and carvacrol interact. The developed nano-formulation could be exploited for controlling different plant diseases and other foodborne pathogens.

Assessment of Pond Productivity in African Catfish Farms

The study was conducted in Coast region specifically in Kibaha, Kisarawe and Bagamoyo Districts. study aimed to determine water quality dynamics, pond characteristics and productivity; and nutritive values of feeds used in catfish farm. Water quality parameters was measured by water proof portable logging multi-parameter meter HANNA MODEL (H198194), feed samples were collected from catfish farmers and proximate analysis was conducted according to standard procedures given in Association of official Analytical Chemists (AOAC,1980), pond characteristics and productivity data were collected through self-administered questionnaires. Results indicated that Bagamoyo had highest temperature (29.94°C±1.70), pH (7.58±0.86) and DO (6.16ppm±0.76). Kisarawe showed highest TDS (1536.12ppm±2236.183) and Salinity (0.74±0.03), Kibaha indicated highest conductivity (1832/Ω/cm±60.69). The CP content was highest in feed sample A (32.96%) and lowest for feed sample E ( 16.85%), Feed C had highest crude fibre CF (11.04%) and sample A had lowest CF (0.36%). Feed A C had lowest EE (3.23%) and highest EE (9.76%) respectively. Highest and lowest fish yield, revenue and profit were recorded in Bagomoyo and Kibaha respectively, highest and lowest FCR were recorded in Kibaha (1.119) and Bagomoyo (0.794) respectively. The highest TDS was recorded in Kisarawe. Government should identify aquaculture zones, give subsidies to seed and feed manufactures so that farmers can incur little cost of production and impose inspections to feeds which are being manufactured.

Empathic disequilibrium in two different measures of empathy predicts autism traits in neurotypical population

BackgroundFeatures of autism spectrum conditions (ASC) are normally distributed within the population, giving rise to the notion of the autism spectrum. One of the hallmark features of ASC is difficulties in social communication, which relies heavily on our ability to empathize with others. Empathy comprises of both cognitive (CE) and emotional (EE) components that, together, allow us to understand another’s emotions and be affected by them appropriately, while maintaining a self-other distinction. Although CE and EE depend on distinct neural and developmental trajectories, it was suggested that the two empathic capacities can influence, balance, and regulate each other. Previous findings regarding the role of emotional and cognitive empathy in ASC have been mixed. Therefore, our study aimed to investigate whether the intra-personal empathy imbalance between the cognitive and emotional components, a measure we termed empathic disequilibrium (ED), can be associated with autism traits at the neurotypical range.MethodsParticipants were 671 young-adults at the neurotypical range who self-reported their empathy, assessed using two highly validated questionnaires—the Interpersonal Reactivity Index and the Empathy Quotient, autism traits using the Autism-Spectrum Quotient, and the related traits, alexithymia, and systemizing.ResultsControlling for the total empathy score, greater ED was found to be positively correlated with autism traits. Specifically, autism traits were found to be elevated in groups of individuals with relatively higher EE than CE, underscoring their imbalance.ConclusionsOur study offers a novel perspective on the understanding of the social difficulties associated with autism tendencies in the general population and has potentially important clinical implications for understanding of ASC. We also propose a novel characterization of autism tendencies based on the imbalance between EE and CE, which we term ED, as opposed to examining EE and CE separately.

Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator.

Adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor is effective against Hepatitis B virus. Its poor oral bioavailability leads to frequent administration causing severe adverse effects. Thereby the entrapment of AD within lipid nanoparticulate systems is a way of increasing AD oral bioavailability as a result of improving intestinal permeability with efficient liver-targeted delivery together with higher drug stability during storage. AD-loaded nanostructured lipid carriers (AD-NLCs) were prepared via solvent emulsification diffusion technique adopting 24 full factorial design to study the effect of lipid percentage, presence of egg yolk lecithin, surfactant type and percentage on entrapment efficiency (E.E.%), particle size and percent in-vitro drug released after 8h (Q8hrs). Formula (F12) showed E.E.% of 90.5 ± 0.2%, vesicle size of 240.2 ± 2.5nm and Q8hrs of 58.55 ± 9.4% was selected as the optimum formula with desirability value of 0.757 based on highest EE%, lowest P.S. and Q8hrs. Further evaluation of the optimized formula using radioiodinated rose bengal (RIRB) in thioacetamide induced liver damage in Swiss Albino mice revealed a higher liver uptake of 22 ± 0.01% ID/g (percent injected dose/g organ) and liver uptake/Blood (T/B) ratio of 2.22 ± 0.067 post 2h of I.V injection of RIRB compared to 9 ± 0.01% ID/g and 0.64 ± 0.017 in untreated group, respectively. NLCs could be successfully used as oral drug delivery carriers of the antiviral drug Adefovir Dipivoxil to the liver with higher stability and oral bioavailability. Graphical abstract.

Novel approaches to cancer therapy with ibuprofen-loaded Eudragit® RS 100 and/or octadecylamine-modified PLGA nanoparticles by assessment of their effects on apoptosis

Objective: The purpose of this study was the design ibuprofen (IBU)-loaded unique Eudragit® RS 100 (ERS) and/or octadecylamine modified PLGA nanoparticles (NPs) for cancer treatment.Significance: The rational for this approach is to bring a new approach to cancer treatment with modification of IBU-loaded PLGA NPs with ERS and/or octadecylamine by means of smaller particle size (PS), cationic surface, biocompatible nature, and investigating their selective efficacy on lung cell lines (A549 lung cancer cell and CCD-19Lu normal cell line).Methods: IBU encapsulated PLGA-based NPs were prepared and characterized for physical and solid-state analyses. In vitro release, MTT, and determination of apoptotic pathways were performed.Results: Considering characterizations, B, C, E, F, H, and K formulations with higher EE%, smaller PS and encouraging higher zeta potential were chosen for further experiments were intended to enhance anticancer action and apoptotic behavior. Formulations were showed biphasic release profile with extended release manner (Korsmeyer–Peppas model with a diffusion-controlled mechanism). The NPs effect on lung cancer cells with high specificity and affinity was demonstrated by MTT study. It was found that the effect of IBU was increased 4–28 times over the pure form. Annexin V-FITC/PI staining method, FITC Active Caspase-3 staining method, and mitochondrial membrane potential detection analyses was performed to determine the apoptotic pathways by flow cytometry.Conclusion: E coded NP is selected as a promising candidate with its highly specific affinity for human lung adenocarcinoma cells and could induce cell death effectively and be a potent system to treat lung cancer.

Gratitude at Work: Prospective Cohort Study of a Web-Based, Single-Exposure Well-Being Intervention for Health Care Workers.

BackgroundEmotional exhaustion (EE) in health care workers is common and consequentially linked to lower quality of care. Effective interventions to address EE are urgently needed.ObjectiveThis randomized single-exposure trial examined the efficacy of a gratitude letter–writing intervention for improving health care workers’ well-being.MethodsA total of 1575 health care workers were randomly assigned to one of two gratitude letter–writing prompts (self- vs other focused) to assess differential efficacy. Assessments of EE, subjective happiness, work-life balance, and tool engagement were collected at baseline and 1-week post intervention. Participants received their EE score at baseline and quartile benchmarking scores. Paired-samples t tests, independent t tests, and correlations explored the efficacy of the intervention. Linguistic Inquiry and Word Count software assessed the linguistic content of the gratitude letters and associations with well-being.ResultsParticipants in both conditions showed significant improvements in EE, happiness, and work-life balance between the intervention and 1-week follow-up (P<.001). The self-focused (vs other) instruction conditions did not differentially predict improvement in any of the measures (P=.91). Tool engagement was high, and participants reporting higher motivation to improve their EE had higher EE at baseline (P<.001) and were more likely to improve EE a week later (P=.03). Linguistic analyses revealed that participants high on EE at baseline used more negative emotion words in their letters (P=.005). Reduction in EE at the 1-week follow-up was predicted at the level of a trend by using fewer first-person (P=.06) and positive emotion words (P=.09). No baseline differences were found between those who completed the follow-up assessment and those who did not (Ps>.05).ConclusionsThis single-exposure gratitude letter–writing intervention appears to be a promising low-cost, brief, and meaningful tool to improve the well-being of health care workers.

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma.

The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and −1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM–QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 °C. Drug release from SIM–QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM–QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.

Biocompatible green tea extract‐stabilised zinc nanoparticles encapsulated by poly(butyl‐2‐cyanoacrylate) with control release profile and antioxidative capacity

SummaryGreen tea extract‐stabilised Zn nanoparticles (GT‐Zn NPs) encapsulated by poly(butyl‐2‐cyanoacrylate) (PBCA@GT‐Zn NPs) were developed for control release of Zn. The crucial parameters, concentrations of GT‐Zn NPs and the monomer n‐butyl‐2‐cyanoacrylate (BCA), which affected the size, polydispersity indexes (PDI) and encapsulation efficiency (EE %), were evaluated to achieve the smaller size, higher EE (%) and stably and uniformly dispersed NPs. The optimised PBCA@GT‐Zn NPs with &lt;100 nm diameter (46.38 ± 3.46 by SEM, 86.91 ± 3.66 by DLS), PDI (0.159 ± 0.042), zeta potential (−20.56 ± 2.53 mV) and EE (89.31 ± 1.09 %) were obtained. In vitro release of Zn ions was conducted at pH 7.4, showing that Zn from the self‐made tablets and lyophilised PBCA@GT‐Zn NPs is released significantly slower than that of GT‐Zn NPs. Additionally, the PBCA@GT‐Zn NP tablets are pH‐responsive, non‐toxic and antioxidative, suggesting that they could be used as safe food material or drug carriers, contributing to relieve Zn deficiency.

Blended, crosslinked alginate-methylcellulose hydrogels for encapsulation and delivery of olfactory ensheathing cells

Transplantation of olfactory ensheathing cells (OECs) is a promising treatment option for spinal cord injuries. Functional outcomes however are highly variable, creating the need for improved transplantation and cell delivery methods. Low OEC survival post-transplantation is primarily due to the absence of a 3D cell delivery system and scaffold, capable of supporting cell structure and migration at the injury site. A 3D cell delivery system, particularly a hydrogel-based system, could ensure viability, functionality and therapeutic activity of transplanted OECs. This study aimed to develop a blended cell delivery system based on alginate (AL) and methylcellulose (MC), capable of encapsulating and delivering OECs over a 20-day period. Three different 1 w/v% ALMC ratios (1:0.5, 1:1 and 1:2) were investigated, which were compared to 1 w/v% AL (control). By chemically crosslinking the pre-gels with CaCl2, OECs were encapsulated within the AL and blended ALMC beads. These beads were then used to study encapsulation efficiency (EE%) and cell delivery, and were further examined with histology and immunocytochemistry. Results showed that the blended ALMC hydrogel can be used to encapsulate OECs, with the highest EE% and cell proliferation exhibited by the 1:0.5 and 1:2 ALMC beads. The 1:1 and 1:2 ALMC beads showed the highest percentage viability for delivered/released and proliferating OECs. Examination of delivered/released OECs concluded that the cell morphology was characteristic of native bipolar OECs, which expressed signature glial markers, demonstrating maintenance of phenotype. In summary, the findings here support the efficacy and use of blended ALMC hydrogels as a cell delivery system.

FORMULATION AND OPTIMIZATION OF TERBINAFINE HCl SOLID LIPID NANOPARTICLES FOR TOPICAL ANTIFUNGAL ACTIVITY

Objective: Solid lipid nanoparticles (SLNs) are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. The aim of this study was to develop and characterize SLNs formulae of Terbinafine HCl (TFH) for topical drug delivery applications.&#x0D; Methods: SLNs were prepared using the solvent injection technique. Glyceryl Monostearate (GMS) served as the lipid base. Three stabilizers; Tween 80, Cremophor RH40, and Poloxamer 188, were used. The effect of stabilizer type and concentration, as well as the lipid concentration, were studied, factorial design of 32*21was applied. The prepared SLNs were characterized regarding their particle size, zeta potential, polydispersity index (PDI), entrapment efficiency percent (EE %), and physicochemical stability. The selected formulae were subjected to further investigations such as morphological studies, in vitro release studies, and Infrared (IR) spectroscopy. They were compared with the marketed cream Lamifen® in term of their antifungal activity against Candida albicans.&#x0D; Results: Lipid concentration, together with the type and concentration of stabilizer, appeared to be the main cornerstones which affect the formation of SLNs. Smaller particle size was observed when increasing the stabilizer concentration and decreasing the lipid concentration. Higher EE% was observed when increasing both the stabilizer and the lipid concentrations. Formulae (F6, F12 andF19) were selected as the most suitable SLNs with optimum particle size of 480.2±18.89, 458.6±12.45 and 246.7±10.5 nm, respectively as well as the highest EE% of 87.13±0.19, 93.69±0.7 and 95.06±0.25, respectively. In vitro microbiological screening of their antifungal activity showed significantly larger zones of inhibition of diameters 25.9±0.25, 25±0.35 and 24.67±0.36 mm, respectively in comparison with the marketed Lamifen® cream which showed a zone of 11.2±0.44 mm diameter.&#x0D; Conclusion: Applying SLNs containing TFH as topical antifungal preparations may be considered as a very promising option as they show good physicochemical characterization with high antifungal activity, which delineates them as a promising dosage form for topical antifungal treatment.

Hierarchical oxygen rich-carbon nanorods: Efficient and durable electrode for all-vanadium redox flow batteries

We describe the fabrication of hierarchical oxygen and nitrogen enriched-carbon electrode materials from zein and polyacrylonitrile by a simple electrospinning technique for durable and high rate all-vanadium redox flow batteries (VRBs). The nitrogen-doped carbon nanorods (NCNR) provide abundant oxygen-rich and nitrogen active sites, and thereby, enhancing the catalytic activity toward both VO2+/VO2+ and V2+/V3+ ion redox reactions by improving ion transfer kinetics and faster electron transfer rate in VRB. With improving electrocatalytic properties, the NCNR decorating carbon felt electrode (NCNR/CF) exhibits excellent battery performance with an impressive specific capacity of 37.3 Ah L−1 than pristine CF (22.8 Ah L−1) and CNR/CF (28.6 Ah L−1) electrodes. The NCNR/CF electrode also shows an outstanding coulombic efficiency (CE, 98.9%) and energy efficiency (EE, 84.3%) compared with the pristine CF (CE, 91.2% and EE, 73.4%) and the CNR/CF (CE, 95.6% and EE, 81.2%) electrodes in the VRB at 40 mA cm−2 current density. Furthermore, the NCNR/CF electrode exhibits 10.9 and 3.1% higher EE as compared to the pristine CF and CNR/CF electrodes, respectively. Therefore, the impressive cyclic rate capability with negligible capacity decay proves the superiority of NCNR as a potential electrode material for all-vanadium redox flow batteries.

The impact of medical student interest in surgery on clerkship performance and career choice

BackgroundInterest in surgery has declined for two decades. This study aimed to evaluate the impact of one’s interest in surgery on career choice. MethodsStudents who completed the surgical clerkship (2016–2017) were invited to complete surveys assessing rotation experience, learning style, burnout, and grit. Students were grouped according to interest or no interest in surgery after the clerkship. ResultsSurveys were completed by 62 students of whom 51.6% reported an interest in surgery. No minority students expressed interest compared with Caucasian (51.1%) and Asian (71.4%) students (p = 0.02). Disinterested students had higher emotional exhaustion (EE, 20 vs 25, p = 0.03). There was no difference in clerkship grade between groups (86.3% vs 85.3%, p = 0.56). Students who matched into surgery had lower EE and higher grit. ConclusionsInterest in surgery was not associated with improved clerkship performance. Disinterested students had higher EE, suggesting interest may play a role in adapting to clerkship challenges.

Preparation and evaluation of optimized zolmitriptan niosomal emulgel

Objective: Novel niosomal formulation may be successfully applied to treat a systemic disease such as migraine through transdermal drug delivery system (TDDS), moreover, the treatment of topical diseases such as mycotic infections by targeting and localizing the drug to the stratum corneum. The current study aims to formulate zolmitriptan (Zt) in niosomal vesicles to potentiate its transdermal effect.Significance: The development of a promising niosomal formulation will push the scaling up of pharmaceutical industry in this field.Methods: Design- Expert 10 was used to design twelve formulations using Box-Behnken. Zt loaded niosomes were prepared by the thin film hydration method using Span 60(S 60), Span 80(S 80) along with cholesterol(Ch) at three different levels. The optimized formulation (F11) was formulated in Emulgel (1:1 emulsion/gel ratio).Results: The vesicles revealed vesicle size (VS) ranging from 133.1 to 851.3 nm, zeta potential (ZP) −43.8 to −82.8 mV, entrapment efficiency (EE%) from 66.7 to 88.7%, and Zt release after 4 h up to 67%. Optimized niosomal formulation (F11) depicted the smallest VS (133.1 nm), highest EE (88.7%), high ZP (−80.6 mV) and satisfactory release after 4 h (61.5%). There was a significant difference (p <.05) in drug permeation after 8 h for niosomal F11(460.98 ug/cm2) and niosomal F11 loaded Emulgel (336.92 ug/cm2) compared to plain Zt loaded emulgel (160.83 ug/cm2). Niosomal F11 loaded emulgel showed thixotropic behavior of rapid recovery, significant bioavailability and pharmacokinetic parameters as compared to the plain Zt-loaded Emulgel.Conclusion: Optimized F11 represents a promising formulation for transdermal drug delivery system to treat both topical and systemic diseases.

Highly Efficient Rh‐catalysts Immobilised by π‐π Stacking for the Asymmetric Hydroformylation of Norbornene under Continuous Flow Conditions

AbstractThe application of C1‐symmetrical diphosphite ligands containing furanose backbone in the Rh‐catalysed asymmetric hydroformylation of norbornene is described. The catalysts were highly active and produced exclusively exo‐norbornanecarboxaldehyde with enantioselectivities (ee) up to 71 %. Considering these promising results, the ligands were modified with a pyrene moiety to accomplish their immobilisation onto carbon materials. The corresponding Rh complexes bearing the novel pyrene‐tagged ligands were synthesised and immobilised onto multiwalled carbon nanotubes (MWCNT), reduced graphene oxide (rGO) and carbon beads (CBs). The novel catalytic systems were tested in the asymmetric hydroformylation of norbornene providing similar performance in terms of both activity and selectivity compared to the non‐immobilised systems. The recyclability of the new heterogenised catalysts was studied in the target reaction in batch mode. Nevertheless, the recycling was unsuccessful due to catalyst leaching. When used under continuous flow mode, these catalysts revealed robust and provided even higher ee than the corresponding homogeneous systems.

Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation, in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68 ± 1.3). All the prepared formulae had particle size less than 500 nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30 mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1 h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn’t exceed 35% during the first hour reaching a 85% of the drug released at the end of 24 h. A7 was selected for the in vivo study; Tmax of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.

Emotional Eating, Health Behaviours, and Obesity in Children: A 12-Country Cross-Sectional Study.

Eating in response to negative emotions (emotional eating, EE) may predispose an individual to obesity. Yet, it is not well known how EE in children is associated with body mass index (BMI) and health behaviours (i.e., diet, physical activity, sleep, and TV-viewing). In the present study, we examined these associations in a cross-sectional sample of 5426 (54% girls) 9–11-year-old children from 12 countries and five continents. EE, food consumption, and TV-viewing were measured using self-administered questionnaires, and physical activity and nocturnal sleep duration were measured with accelerometers. BMI was calculated using measured weights and heights. EE factor scores were computed using confirmatory factor analysis, and dietary patterns were identified using principal components analysis. The associations of EE with health behaviours and BMI z-scores were analyzed using multilevel models including age, gender, and household income as covariates. EE was positively and consistently (across 12 study sites) associated with an unhealthy dietary pattern (β = 0.29, SE = 0.02, p < 0.0001), suggesting that the association is not restricted to Western countries. Positive associations between EE and physical activity and TV viewing were not consistent across sites. Results tended to be similar in boys and girls. EE was unrelated to BMI in this sample, but prospective studies are needed to determine whether higher EE in children predicts the development of undesirable dietary patterns and obesity over time.

Enzyme nanovehicles: Histaminase and catalase delivered in nanoparticulate chitosan

Widespread skin allergies are of high societal concern. This pathology usually includes “histamine intolerance” and inflammatory processes affecting the skin. Oxidative stress, due to both intrinsic and environmental factors, leads to skin disorders, disease, and aging. Since the stratum corneum (SC) allows only small, lipophilic molecules to be absorbed through the skin, proteins, which are large amphoteric macromolecules, display limited bioavailability. The present study investigates the potential of chitosan nanoparticles as vehicle for two enzymes (catalytic proteins): catalase (CAT) and diamine oxidase (histaminase, DAO). Chitosan is an inexpensive, biocompatible, biodegradable, mucoadhesive, antibacterial, and antifungal biopolymer. Chitosan nanoparticles (CNP) have a high surface to volume ratio, hence high surface charge density and stronger biological activity than chitosan itself. CNP encapsulating DAO/CAT were prepared by using chitosans from different sources (shrimp and fungal). Nanoparticles were prepared by ionic complexation with sodium tripolyphosphate (TPP). Two different protein concentrations (0.5 mg/mL and 1.0 mg/mL) were investigated in the preparation of the nanoparticles. The resulting CNP were characterized by size (from 200 to 300 nm) and zeta potential (up to 9 mV) measurements, encapsulation efficiency (EE, up to 48%), loading capacity (LC, up to 42%), ratio of residual amino groups (RRAG, up to 14%), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and residual enzymatic activity. The antioxidant activity of the CNP encapsulating CAT was evaluated as well. The kinetics of protein release from the nanocomposites was monitored spectrophotometrically (for 160 h). Here we report that CAT was encapsulated with higher EE and residual enzymatic activity, while encapsulated DAO displayed better release profiles. Following encapsulation and release from CNP, both enzymes retained activity. The activities of DAO/CAT remained constant after five months in storage at −20 °C. These findings show that tailored nanosized chitosan affords enhancement to enzymes with low activity (like DAO) and shows promise as a carrier for therapeutic enzymes. Further investigations into its capability to increase their bioavailability are warranted.

Left atrium function and deformation in very preterm infants with and without volume load

Left atrium (LA) function can be assessed by volumetric measurements, conventional and tissue Doppler, and more recently, deformation imaging using two-dimensional speckle tracking echocardiography (2DSTE). 2DSTE allows for measurement of volume and deformation and can quantify the contribution of the reservoir, conduit, and contraction phase. A common cause for LA dysfunction in very preterm infants is volume overload with a patent ductus arteriosus (PDA). The aim of this study was to explore the feasibility and reliability of LA 2DSTE in preterm infants, and describe LA function with and without PDA volume load. We prospectively recruited preterm infants <30weeks of gestation referred for assessment of a possible PDA. A cardiac ultrasound was performed at day 3 and in week 4 of life and analyzed using conventional techniques and 2DSTE. Forty-eight infants (32 with PDA) were included. LA 2DSTE analysis was feasible in 96% of measurements with good reliability of strain and volume parameters. Strain rate was less reliable. Poorer LA contraction and reservoir function was associated with larger LA volume index, higher inflow over the mitral valve at early diastole, higher EA ratio, and higher Ee' ratio. Poorer conduit function was associated with higher Ee' ratio. A larger PDA diameter was found to be an independent contributor to deteriorating LA contraction and reservoir function. LA 2DSTE analysis is feasible in preterm infants and provides detailed information on atrium mechanics. Further studies are needed to explore the clinical value of these new parameters in this population.