Investigating a Vitamin D Delivery Toothpaste Using a Penetration Enhancer Compound

Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.

Preliminary phytochemical analysis,antibacterial,antifungal and anticandidal activities of successive extracts of Crossandra infundibuliformis

Objective:To investigate the phytochemical,antibacterial,antifungal and anticandidal activity of successive extracts of Crossandra infundibuliformis(Acanthaceae) leaves.Methods:Preliminary screening on the presence of alkaloids,saponins,phytosterols,phenolic compounds,flavanoids, tannins,carbohydrates,terpenoids,oils and fats were carried out by phytochemical analysis.The antibacterial,antifungal and anticandidal activities were done by agar well diffusion technique. Results:The successive extracts have an array of chemical constituents and the MIC values of antibacterial activity ranges from 0.007 8 to 0.015 0μg/mL.In case of antifungal and anticandidal activities the MIC values were between 0.125 and 0.250μg/mL.Conclusions:These findings demonstrate that the leaf extracts of C.infimdibuliformis presents excellent antimicrobial activities and thus have great potential as a source for natural health care products.

Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment.RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

Screening and characterization of extracelluar L-asparaginase producing Bacillus subtilis strain hswx88,isolated from Taptapani hotspring of odisha,India

Objective:To screen and isolate an eco-friendly,u thermophilic and potent L-asparaginase producing bacterium,with novel immunological properties that may obviates hypersensitivity reactions.Methods:In the present study baclerial strain isolated for extracellular L-asparaginase production from hotspring,identified by morphological,biochemical and physiological tests followed by t6S rDNA technology and the L-asparaginase production ability was tested by both semi quantitative and quantitative enzymatic assay.Result:The bacterial strain was identified as Bacillus sublilis strain hswx88(GenBank Accession Number JQ237656.1).The extracellular enzyme yielding capacity isolate Bacillus subtilis strain hswx88(23.8 IU/mL)was found to be 1.7 and 14.5 limes higher than the reference organism Pectobacterium carotovorum MTCC 1428(14.2 IU/mL)and Bacillus sp.BCCS 034(1.64 IU/mL).Conclusion:The isolate is eco-friendly and useful to produce bulk quantity of extracellular,thermophilic L-asparaginase for the treatment of various tumor cases and for preparation of acrylamide free fry food preparation.

Validated gradient stability indicating HPLC method for determining Diltiazem Hydrochloride and related substances in bulk drug and novel tablet formulation

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.

Free radical scavenging and reducing power of Lawsonia inermis L.seeds

Objective:To determine the antioxidant activity,total phenolic and flavonoid content of Petroleum ether extract（PE）,Dichloromethane extract（DCM）,Ethanol extract（ET） and aqueous extract（AQ） of henna seeds.Methods:Total antioxidant assay（phosphomolybenum method）, DPPH radical scavenging assay,reducing power assay and lipid peroxidation inhibition assay were used to ascertain the potential of seeds as an antioxidant.Results:In all the assays carried out ET showed a greater potential to scavenge DPPH radical,reduce MO（Ⅳ） to MO（Ⅴ） complex and Fe（Ⅲ） to Fe（Ⅱ） and to inhibit lipid peroxidation.The IC50 of ET was far greater than that of the standard,ascorbic acid（AS） in the lipid peroxidation assay.The activity of AQ was lesser when compared with that of ET but greater than PE and DCM.The amount of phenolics and flavonoids were present in higher amounts in ET followed by AQ.Trace amounts of phenolics were detected in PE and DCM,but the amount of flavonoids were below the detection level.The study showed that the antioxidant activity and the concentrations of phenolics and flavonoids are proportionate to each other.Conclusions:Ethanolic extract of henna seeds are efficient antioxidants,which can be utilized for further isolation of active compounds and pharmaceutical applications.

Evaluation of the analgesic activity of ethyl acetate,methanol and aqueous extracts of Pleurotus eous mushroom

Objective:To evaluate the analgesic activity of the ethyl acetate,methanol and aqueous extracts of Plewotus eous(P.eous) mushroom.Methods:The dried fruiting bodies were extracted with ethyl acetate,methanol and water.The analgesic effect of extracts of P.eous were investigated at doses 250 500 and 1 000 mg/kg body weight,using acetic-acid induced writhing,hot-plate,tail immersion and tail-clip tests.Results:P.eous extracts produced significant reduction in number of writhes induced by intraperitoneal injection of acetic-acid(P【0.05).Moreover,in hot-plate and tail immersion test,all the three extracts significantly raised the pain threshold at different time of observation(0-60 min) in comparison with control(P【0.05).In tail-clip test the extracts also caused a significant inhibition of pain at both the doses used(P【0.05).Conclusions:The results of present study suggest that extracts of P.eous possess potent analgesic property and could serve as a base for future drugs.

Hepatoprotective potential of petroleum ether leaf extract of Crossandra infundibuliformis on CCl_4 induced liver toxicity in albino mice

Objective:To analyze the hepatoprotective effect of the Crossandra infundibuliformis.Methods: Hepatotoxicity was induced by carbon tetrachloride.Petroleum ether extract of dried leaves was administrated to mice for 7 days.The hepatoprotective effect of petroleum ether extract was evaluated by the assay of liver function biochemical parameters.Results:The result clearly indicates that petroleum ether extract showed significant hepatoprotection when compared with standard Silumarin.Conclusions:The petroleum ether extract of the leaves of Crossandra infundibuliformis possess significant acute hepatoprotective activity.Thus further investigation on this species would bring a promising drug for liver disorders.

Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.

液相色谱-飞行时间质谱、液相色谱-串联质谱和核磁共振用于右旋兰索拉唑的强制降解研究和氧化降解产物的结构表征(英文)

The present study deals with the forced degradation behavior of dexlansoprazole under International Conference on Harmonisation(ICH)prescribed stress conditions. The drug was found to be more labile under acid,base,neutral,oxidative hydrolysis and thermal stress,while it was moderately stable under photolytic conditions. The known and unknown degradation products were separated on a C-18 column using a stabilityindicating method. Liquid chromatography-mass spectrometry(LC-MS)analysis was performed for all the degradation studies. Isolation and structure characterization of oxidation degradation products were executed using sophisticated tools,viz. preparative high performance liquid chromatography(HPLC),liquid chromatographymass spectrometry / time of flight(LC-MS / TOF),liquid chromatography-tandem mass spectrometry(LC-MS /MS),and nuclear magnetic resonance(NMR). This study demonstrates an ample methodology of degradation studies and structure elucidation of unknown degradation products of dexlansoprazole,which helps in the development and stability study of active pharmaceutical ingredients and formulated products.

Phytochemical Analysis and Antifungal Activity of Extracts from Leaves and Fruit Residues of Brazilian Savanna Plants Aiming Its Use as Safe Fungicides

The increasing demand for safe food without preservatives or pesticides residues has encouraged several studies on natural products with antifungal activity and low toxicity.In this study,ethanolic extracts from leaves and fruit residues(peel and seeds)of three Brazilian savanna species(Acrocomia aculeata,Campomanesia adamantium and Caryocar brasiliense)were evaluated against phytopathogenic fungi.Additionally,the most active extract was chemically characterized by ESI-MS and its oral acute toxicity was evaluated.Extracts from C.brasiliense(pequi)peel and leaves were active against Alternaria alternata,Alternaria solani and Venturia pirina with minimal inhibitory concentrations between 350 and 1000 lg/mL.When incorporated in solid media,these extracts extended the lag phase of A.alternata and A.solani and reduced the growth rate of A.solani.Pequi peel extract showed better antifungal activity and their ESI-MS analysis revealed the presence of substances widely reported as antifungal such as gallic acid,quinic acid,ellagic acid,glucogalin and corilagin.The oral acute toxicity was relatively low,being considered safe for use as a potential natural fungicide.

Surging footprints of mathematical modeling for prediction of transdermal permeability

In vivo skin permeation studies are considered gold standard but are difficult to perform and evaluate due to ethical issues and complexity of process involved. In recent past, a useful tool has been developed by combining the computational modeling and experimental data for expounding biological complexity. Modeling of percutaneous permeation studies provides an ethical and viable alternative to laboratory experimentation. Scientists are exploring complex models in magnificent details with advancement in computational power and technology. Mathematical models of skin permeability are highly relevant with respect to transdermal drug delivery, assessment of dermal exposure to industrial and environmental hazards as well as in developing fundamental understanding of biotransport processes.Present review focuses on various mathematical models developed till now for the transdermal drug delivery along with their applications.

Reversible antispermatogenic and antisteroidogenic activities of Feronia limonia fruit pulp in adult male rats

Objective:To explore the antispermatogenic and testicular antisleroidogenic activities of Feronia limonia fruit pulp southern India.Methods:Fourty Wistar male albino rats(Ratios norvegicus)were equally divided into four groups.Experimental groups were administered with the ethanolic extract of Feronia lirnonia(F.limoni)fruit pulp at doses of 250 and 500 nig/kg body weight once daily for 55 days.All treated rats had corresponding recovery groups.At the end of each treatment periods,various spermatological indices,tissue biochemicals and testicular enzymes levels were analysed.Blood profiles were also estimated.Results:Compared with the control,the F.lirnonia.fruit pulp at both dose leveb did not decrease body weight,which were associated with decline in epididymal sperm count,motility,viability and increased percent of abnormal sperm.Further,F.limonia.fruit pulp at 500 mg/kg body weight markedly reduced the epididymal and testicular protein content by 24.58%and 29.86%,respectively,as well as the glucose-6-phosphate dehydrogenase and△~5-3β-hydroxy steroid dehydrogenase)levels by 42.82%and 38.08%,respectively,while a significant elevation was observed in testicular cholesterol and ascorbic acid content.A gradual recovery of all parameters was observed after 55 days of treatment withdrawal.No significant alterations in haematological indices were observed.Conclusions:The present findings indicate that F.lirnonia fruit pulp may have reversible antispermatogenic and antisteroidogenic properties,and could partially support the traditional use as mate contraceptive.

Preliminary study on antifertility activity of Enicostemma axillare leaves and Urena lobata root used in Indian traditional folk medicine

Objective:To evaluate the possible antifertility activity of Enicostemma axillare(E.axillare) leaves and Urena lobata(U.lobata) root in adult male Wistar albino rats.Methods:Six groups of rats were treated with ethanolic(70%v/v) extracts of E.axillare(375 and 750 mg/kg body weight) and U.lobata root(300 and 600 mg/kg body weight) once daily for 55 days.Control groups received the distilled water and vehicle.All the treated rats had corresponding recovery groups.At the end of each treatment periods,animals were killed and organ weights,sperm characteristics,testicular and epididymal biochemicals as well as testicular enzymes were assessed.Results:The E. axillare and U.lobata at tested doses did not decrease body weight,whereas the weight of testes, epididymides and seminal vesicles were significantly(P【0.01) reduced.Significantly(P【0.01) more reductions in the sperm motility,viability and counts,epididymal and testicular protein contents were noted in the rats treated with higher dose of both the plants.Both the plants at the higher dose caused a marked increase(P【0.01) in sperm morphological abnormalities,testicular cholesterol and ascorbic acid contents were remarkably increased(P【0.01),while,the activities of testicular glucose-6-phosphate dehydrogenase(G-6-PDH) andΔ~5-3β-hydroxy steroid dehydrogenase(Δ~5-3β-HSD) were significantly reduced(P【0.01).However,reversal of these changes occurred after 55 days of treatment withdrawal.Conclusions:This study suggests that the ? axillare leaves and U.lobata root reversibly inhibited spermatogenesis and steroidogenesis indicating reversible antifertility activity which could partially support the traditional of these plants as male contraceptives.

Characterization of Polyvinyl Pyrollidone Coated Sodium Borohydride Stabilized Particle Colloidal Silver Fresh None Filtered and Nano Filtered Solution Made up of Magnetic Stirring and Cooling Method

Characterization is absolutely necessary and is a must in order to understand and estimate different silver nanoparticle (nm) size in specific group wise manner which corresponds to group wise in number & sizes, and their importance and effect on biological tissue and organs with agglomeration for nano toxicological studies in environments, the acute toxicity of colloidal silver nano particles (AgNps) were studied in fresh dissected tissues of Swiss Albino mice and their fetuses. In this manuscript, an attempt is made to demonstrate the synthesis and characterization of silver nano particles with a wide range of sizes (from 2.75 nm up to 1908.2 nm in radius) by reducing silver nitrate powder with polyvinyl pyrollidone in aqueous solutions in the presence of a sodium borohydride stabilizer. The resulting particles were found spherical aggregates with a rough surface and poly dispersity index below 18.26% (>0.783 PDI). The particle optical, cumulative, diluents and electrical conductivity properties were examined by dynamic light scattering and zeta potential but morphology was evaluated after examination by transmission electron microscopy & image-j. Silver nanoparticles were directly coated with polyvinyl pyrollidone with a sodium borohydride stabilizer. Optical properties on a single-particle level were studied by means of auto correlation function measurements. The effective poly dispersity index of the charged silver nanoparticles was low enough to form a colloidal crystal at low ionic strength. Colloidal form is found more toxic than suspended particles in 1.5 molar sodium chloride solution;this shows increase of silver nanoparticles size due to agglomeration, will reduce the toxicity but increase teratogenicity.

Fungi and insects as models of extraordinary symbiosis

Symbiosis among microorganisms represents an interesting relationship that takes different shapes.Obligatory,facultative,and endosymbiotic relationships have all been reported between different microorganisms.Whether it is mutualism,commensalism,amensalism,or parasitism,understanding every association is of great importance to science and humanity.Knowing how these creatures benefit from each other may be useful for biocontrol purposes,or even for discovery of novel metabolites that result from these associations,and which may not be produced by the individual species.In this review,five examples of symbiosis were presented,including among the Laboulbeniales;Septobasidium;Ambrosia Fungi and Beetles;Leaf-cutter ants and their fungus gardens;and finally,termites and Termitomyces.Moreover,the benefits each partner is getting were highlighted,and uniqueness in every form of those symbiosis models was simply described.

The coral mushrooms Ramaria and Clavaria

The need to improve the quality life together with the increase in the frequency of threating diseases direct the attention of many scientists to look for potential foods as a source of nutritional and therapeutical agents.Since ancient times,several mushrooms have been reported as a nutritious food with valuable medicinal properties.The genus Ramaria and Clavaria belonging to coral fungi are a group of edible mushrooms that are distributed all over the world.The studies on different species of Ramaria and Clavaria have revealed their medicinal potentials.This review aims to present the importance of genera Ramaria and Clavaria as both food and medicine,and they offer new insights to researchers to develop new drugs and nutraceuticals.

Convergence of nanomedicine and neutrophils for drug delivery

Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology that has enormous advantages in improving treatment efficacy and reducing side effects,neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles employed in precise therapeutic interventions by either coating nanoparticles with their membranes,loading nanoparticles inside living cells,or engineering chimeric antigen receptor(CAR)-neutrophils.These neutrophil-inspired therapies have shown superior biocompatibility,targeting ability,and therapeutic robustness.In this review,we summarized the benefits of combining neutrophils and nanotechnologies,the design principles and underlying mechanisms,and various applications in disease treatments.The challenges and prospects for neutrophil-based drug delivery systems were also discussed.

Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

Inflammatory bowel disease(IBD)is inflammatory intestinal disorders associated with dysregulated gut microbiota.Bacteriotherapy that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat IBD.Orally delivered probiotics,such as Escherichia coli Nissle 1917(EcN),can produce beneficial ingredients,competitively inhibit the proliferation of pathogens,and promote the restoration of gut microbiome homeostasis.However,environmental stresses(such as gastric acids)in the gastrointestinal(GI)tract pose an enormous challenge to the probiotics following oral administration,leading to decreases in viability and activity of probiotics.Meanwhile,the inferior mucoadhesive capability of probiotics results in low colonization efficacy,further compromising their therapeutic effect.Coating probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI tract.Here,we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan(CS)and immunomodulatory hyaluronic acid(HA)to generate HA-CS-EcN.These biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI tract.The probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of IBD.Collectively,this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

Innovative hydrogel-based delivery systems for immunotherapy:A review of pre-clinical progress

Immunotherapy has markedly reinvented how we treat cancer,as shown by numerous Food and Drug Administration(FDA)drug approvals that have made significant clinical impact and ongoing clinical trials.However,undesirable side effects,such as autoimmunity and inflammation,and inconsistent clinical outcomes remain a major challenge.Improving response rates across various immunotherapeutic reagents is imperative to enhance overall effectiveness and reduce adverse side effects.To address this challenge,interdisciplinary approaches have been explored by incorporating immunotherapies into hydrogels,enabling finecontrolled delivery to target tissues.This review focuses on recent progress in the utilization of hydrogel-based delivery systems for cancer immunotherapy and their potential to further enhance treatment response rates.Specifically,recent preclinical advances in hydrogels implemented with immune checkpoint inhibitors,combination therapies,and vaccines,along with selfassembled peptide hydrogels,are reviewed.We also discuss technological advances and drawbacks in this area and provide insights to ultimately realize the clinical application of hydrogels in cancer immunotherapy.