Search results for: anti-biofilm drug activity screening

Authors: Michelle Nighswander

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Suicide can be a tragic response to mental illness. It is difficult for people to disclose or discuss suicidal impulses. The stigma surrounding mental health can create a reluctance to seek help for mental illness. Patients may feel pressure to exhibit a socially desirable demeanor rather than reveal these issues, especially if they sense their healthcare provider is pressed for time or does not have an extensive history with their provider. Overcoming these barriers can be challenging. Although there are several validated depression and suicide risk instruments, varying processes used to administer these tools may impact the truthfulness of the responses. A literature review was conducted to find evidence of the impact of the environment on the accuracy of depression screening. Many investigations do not describe the environment and fewer studies use a comparison design. However, three studies demonstrated that computerized self-reporting might be more likely to elicit truthful and accurate responses due to increased privacy when responding compared to a face-to-face interview. These studies showed patients reported positive reactions to computerized screening for other stigmatizing health conditions such as alcohol use during pregnancy. Computerized self-screening for depression offers the possibility of more privacy and patient reflection, which could then send a targeted message of risk to the healthcare provider. This could potentially increase the accuracy while also increasing time efficiency for the clinic. Considering the persistent effects of mental health stigma, how these screening questions are posed can impact patients’ responses. This literature review analyzes trends in depression screening methodologies, the impact of setting on the results and how this may assist in overcoming one barrier caused by stigma.

Keywords: computerized self-report, depression, mental health stigma, suicide risk

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Authors: Priyanka Sharma, Ranjita Das, Mohan C. Kalita, Debajit Thakur

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Background: Actinomycetes are the richest source of novel bioactive secondary metabolites such as antibiotics, enzymes and other therapeutically useful metabolites with diverse biological activities. The present study aims at the antimicrobial potential and genetic diversity of culturable Actinomycetes isolated from protected forest ecosystems of Assam which includes Kaziranga National Park (26°30˝-26°45˝N and 93°08˝-93°36˝E), Pobitora Wildlife Sanctuary (26º12˝-26º16˝N and 91º58˝-92º05˝E) and Gibbon Wildlife Sanctuary (26˚40˝-26˚45˝N and 94˚20˝-94˚25˝E) which are located in the North-eastern part of India. Northeast India is a part of the Indo-Burma mega biodiversity hotspot and most of the protected forests of this region are still unexplored for the isolation of effective antibiotic-producing Actinomycetes. Thus, there is tremendous possibility that these virgin forests could be a potential storehouse of novel microorganisms, particularly Actinomycetes, exhibiting diverse biological properties. Methodology: Soil samples were collected from different ecological niches of the protected forest ecosystems of Assam and Actinomycetes were isolated by serial dilution spread plate technique using five selective isolation media. Preliminary screening of Actinomycetes for an antimicrobial activity was done by spot inoculation method and the secondary screening by disc diffusion method against several test pathogens, including multidrug resistant Staphylococcus aureus (MRSA). The strains were further screened for the presence of antibiotic synthetic genes such as type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and non-ribosomal peptide synthetases (NRPS) genes. Genetic diversity of the Actinomycetes producing antimicrobial metabolites was analyzed through 16S rDNA-RFLP using Hinf1 restriction endonuclease. Results: Based on the phenotypic characterization, a total of 172 morphologically distinct Actinomycetes were isolated and screened for antimicrobial activity by spot inoculation method on agar medium. Among the strains tested, 102 (59.3%) strains showed activity against Gram-positive bacteria, 98 (56.97%) against Gram-negative bacteria, 92 (53.48%) against Candida albicans MTCC 227 and 130 (75.58%) strains showed activity against at least one of the test pathogens. Twelve Actinomycetes exhibited broad spectrum antimicrobial activity in the secondary screening. The taxonomic identification of these twelve strains by 16S rDNA sequencing revealed that Streptomyces was found to be the predominant genus. The PKS-I, PKS-II and NRPS genes detection indicated diverse bioactive products of these twelve Actinomycetes. Genetic diversity by 16S rDNA-RFLP indicated that Streptomyces was the dominant genus amongst the antimicrobial metabolite producing Actinomycetes. Conclusion: These findings imply that Actinomycetes from the protected forest ecosystems of Assam, India, are a potential source of bioactive secondary metabolites. These areas are as yet poorly studied and represent diverse and largely unscreened ecosystem for the isolation of potent Actinomycetes producing antimicrobial secondary metabolites. Detailed characterization of the bioactive Actinomycetes as well as purification and structure elucidation of the bioactive compounds from the potent Actinomycetes is the subject of ongoing investigation. Thus, to exploit Actinomycetes from such unexplored forest ecosystems is a way to develop bioactive products.

Keywords: Actinomycetes, antimicrobial activity, forest ecosystems, RFLP

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

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We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

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Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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Authors: Sutapa Mondal Roy, Suban K. Sahoo

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The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.

Keywords: silver nanoparticles, ciprofloxacin, density functional theory, drug delivery

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Rajinikanth Siddalingam, Poonguzhali Subramanian

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The present study aims to prepare and evaluate the self-nano emulsifying drug delivery (SNEDDS) system to enhance the dissolution rate of a poorly soluble drug dutasteride. The formulation was prepared using capryol PGMC, Cremophor EL, and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to find out the nano emulsification range and also to evaluate the effect of dutasteride on the emulsification behavior of the phases. Prepared SNEDDS formulations were evaluated for its particle size distribution, nano emulsifying properties, robustness to dilution, self-emulsification time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze-thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The particle size, zeta potential and polydispersity index of the optimized formulation found to be 35.45 nm, -15.45 and 0.19, respectively. The in vitro results are revealed that the prepared formulation enhanced the dissolution rate of dutasteride significantly as compared with pure drug. The in vivo studies in was conducted using rats and the results are revealed that SNEDDS formulation has enhanced the bioavailability of dutasteride drug significantly as compared with raw drug. Based the results, it was concluded that the dutasteride-loaded SNEDDS shows potential to enhance the dissolution of dutasteride, thus improving the bioavailability and therapeutic effects.

Keywords: self-emulsifying drug delivery system, dutasteride, enhancement of bioavailability, dissolution enhancement

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Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

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Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

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Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

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The number of products based on new drug delivery systems has significantly increased in the past few years, and this growth is expected to continue in the near future. These biopharmaceuticals present challenges to drug delivery scientists because of their unique nature and difficulty in delivery through conventional routes. Therefore, future research will focus on the delivery of these complex molecules through different routes, including oral, nasal, pulmonary, vaginal, rectal, etc. The aim of present study was to formulate and evaluate ethosomes of Plumeria indica flowers which may deliver the drug to targeted site more efficiently than marketed preparation and also overcome the problems related with oral administration of drug. The formulations were prepared with ethanol, lecithin, propylene glycol and were evaluated.

Keywords: ethosomes, herbal extract, plumeria alba, lecithin

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Cesar Torres, Robert Briber, Nam Sun Wang

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Eye drops are the most commonly used treatment for short-term and long-term ophthalmic diseases. However, eye drops could deliver only about 5% of the functional ingredients contained in a burst dosage. To address the limitations of eye drops, the use of therapeutic contact lenses has been introduced. Drug-loaded contact lenses provide drugs a longer residence time in the tear film and hence, decrease the potential risk of side effects. Nevertheless, a major limitation of contact lenses as drug delivery devices is that most of the drug absorbed is released within the first few hours. This fact limits their use for extended release. The present study demonstrates the application of long-alkyl chain ionic surfactants on extending drug release kinetics from commercially available silicone hydrogel contact lenses. In vitro release experiments were carried by immersing drug-containing contact lenses in phosphate buffer saline at physiological pH. The drug concentration as a function of time was monitored using ultraviolet-visible spectroscopy. The results of the study demonstrate that release kinetics is dependent on the ionic surfactant weight percent in the contact lenses, and on the length of the hydrophobic alkyl chain of the ionic surfactants. The use of ionic surfactants in contact lenses can extend the delivery of drugs from a few hours to a few weeks, depending on the physicochemical properties of the drugs. Contact lenses embedded with ionic surfactants could be potential biomaterials to be used for extended drug delivery and in the treatment of ophthalmic diseases. However, ocular irritation and toxicity studies would be needed to evaluate the safety of the approach.

Keywords: contact lenses, drug delivery, controlled release, ionic surfactant

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Authors: Atefeh Ahmadi, Mohamed Sharif Mustaffa

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Mental health problems that children introspect them are hardly identified. The internalizing nature of Anxiety Disorders as the most prevalent psychological diseases, make them been under recognized by parents and teachers and so become under attended by school counsellors and subsequently under referred to clinicians. The aim of this study is to investigate the level of Anxiety Disorders to clarify if it is necessary to run screening programs in rural educational settings. Spence children anxiety scale-malay-child for the first time in Malaysia distributed among 640 Malay rural primary school students aged from 9-11 years old. Cut-off score was considered one standard deviation more than the mean of all students’ scores. The results of descriptive analyses revealed the mean for scores of SCAS was 32.84 and 15.6% of students had high level of anxiety. In addition, the level and prevalence of six types of anxiety disorders based on SCAS were described. In regards to the study outcomes, screening for anxiety disorders in academic settings could prevent and reduce their side effects by early identification.

Keywords: anxiety disorders, primary schools, SCAS, screening

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Chia-Hsun Chang

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Background: Combination of drug treatment, dietary management, and regular exercise can effectively control type II diabetes mellitus (T2DM). Performing daily physical activities other than structured exercise is much easier and whether daily physical activities including work, walking, housework, gardening, leisure exercise, or transportation have a similar effect on diabetes control is not well studied.Aims and Objectives: This study aims to determine whether daily physical activity undertaken by patients with T2DM is associated with their diabetes control. Design: A correlation study with prospective design. Methods: Purposive sampling of 206 patients with T2DM was recruited from a medical center in Central Taiwan. The International Physical Activity Questionnaire was used to assess daily levels of physical activities, and the Diabetes Compliance Questionnaire was used to assess medication and dietary compliance. Data of diabetes control (hemoglobin A1c, HbA1c)were followed up every three months for one year after recruitment. Results: In this study, the average age of the participants was 62.5 years (±10.4 years), and the average duration of diabetes since diagnosis was 13.2 years (±7.8), 112 of the participants were women (54.4%) and 94 of the participants were men (45.6%). The mean HbA1c level was 7.8% (±1.4), and 78.2% of the participants presented with unsatisfactory diabetes control. Because the participants were distributed across a wide age range, and their physical health, activity levels, and comorbidities might have varied with age, the participants were divided into two groups: 121 participants who were younger than 65 years (58.7%) and 85 participants who were older than 65 years (41.3%). Both younger (< 65 years) and older (> 65 years) patients with diabetes engaged in more moderate and low levels of physical activity (89.3% and 87%, respectively). Results showed that the levels of daily physical activity were not significantly associated with diabetes control after adjustment for medication and dietary compliance in both groups. Conclusion: Performing daily physical activity is not significantly correlated with diabetes control. Daily physical activity cannot completely replace exercise. Relevance to Clinical Practice: Health personnel must encourage patients to engage in exercise that is planned, structured, and repetitive for improving diabetes control.

Keywords: daily physical activity, diabetes control, international physical activity questionnaire (IPAQ), type II diabetes mellitus (T2DM)

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Authors: Afaf Abdallah, Moawia Elsadig

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Background: Cervical cancer is the second most common women cancer among worldwide; representing 13% of female cancers. In Sudan, it ranks as the second most frequent cancer among women as other developing countries. Aim: Is to study awareness, attitude of nursing students towards cervical cancer prevention. The results: Most of the students were not aware of other screening methods than Pap smear test. However, half of the respondents showed positive attitudes towards HPV vaccination. More than two-thirds of respondents exhibited a positive attitude and were willing to undergo Pap smear in the future. Conclusion: The study shows that the majority of the participants have poor information, education would motivate nurses to participate actively in awareness raising, screening, and management.

Keywords: cervical cancer, knowledge, attitude, screening

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Authors: Ikram Mohamed Eltayeb Elsiddig, Yacouba Amina Djamila, Amna El Hassan Hamad

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Hyperglycemia and diabetes have been treated with several medicinal plants for a long time, meanwhile reduce associated side effects than the synthetic ones. Therefore, the search for more effective and safer anti-diabetic agents derived from plants has become an interest area of active research. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol, and high blood pressure. The present study was carried out to investigate the anti-hyperglycemic effect of the extracts of A. sativum bulb growing in Sudan on glucose-loaded Wistar albino rats. A. sativum bulbs were collected from local vegetable market at Khourtoum/ Sudan in a fresh form, identified and authenticated by taxonomist, then dried, and extracted with solvents of increasing polarity: petroleum ether, chloroform, ethyl acetate and methanol by using Soxhlet apparatus. The effect of the extracts on glucose uptake was evaluated by using the isolated rats hemidiaphgrams after loading the fasting rats with glucose, and the anti-hyperglycemic effect was investigated on glucose-loaded Wistar albino rats. Their effects were compared to control rats administered with the vehicle and to a standard group administered with Metformin standard drug. The most active extract was analyzed chemically using GC-MS analysis compared to NIST library. The results showed significant anti-diabetic effect of extracts of A. sativum bulb growing in Sudan. Addition to the hypoglycemic activity of A. sativum extracts was found to be decreased with increase in the polarity of the extraction solvent; this may explain the less polarity of substance responsible for the activity and their concentration decreased with polarity increase. The petroleum ether extract possess anti-hyperglycemic activity more significant than the other extracts and the Metformin standard drug with p-value 0.000** of 400mg/kg at 1 hour, 2 hour and four hour; and p-value 0.019*, 0.015* and 0.010* of 200mg/kg at 1 hour, 2 hour and four hour respectively. The GC-MS analysis of petroleum ether extract, with highest anti -diabetes activity showed the presence of Methyl linolate (42.75%), Hexadecanoic acid, methyl ester (10.54%), Methyl α-linolenate (8.36%), Dotriacontane (6.83), Tetrapentacontane (6.33), Methyl 18-methylnonadecanoate (4.8), Phenol,2,2’-methylenebis[6-(1,1-dimethylethyl)-4-methyl] (3.25), Methyl 20-methyl-heneicosanoate (2.70), Pentatriacontane (2.13) and many other minor compounds. The most of these compounds are well known for their anti-diabetic activity. The study concluded that A. sativum bulbs extracts were found to enhanced the reuptake of glucose in the isolated rat hemidiaphragm and have antihyperglycemic effect when evaluated on glucose-loaded albino rats with petroleum ether extract activity more significant than the Metformin standard drug.

Keywords: Allium, anti-hyperglycemic, bulbs, sativum

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

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Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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Authors: Nitin Dwivedi, Jigna Shah

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Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Shilpa Bhilegaonkar, Ram Gaud

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Candesartan cilexetil is a poorly soluble antihypertensive agent with solubility limited bioavailability (15%). To initiate process of solubilisation, it is very much necessary to displace the air at the surface and wet the drug surface with a solvent, with which drug is compatible. Present research adopts the same principle to improve solubility and dissolution of candesartan cilexetil. Solvents used here are surfactant and modified surfactant in different drug: solvent (1:1-1:9) ratio’s for preparation of adsorbates. Adsorbates were then converted into free flowing powders as liquisolid compacts and compressed to form tablets. Liquisolid compacts were evaluated for improvement in saturation solubility and dissolution of candesartan cilexetil. All systems were evaluated for improvement in saturation solubility and dissolution in different medias such as water, 0.1 N HCl, Phosphate buffer pH 6.8 and media given by office of generic drugs along with other physicochemical testing. All systems exhibited a promising advantage in terms of solubility and dissolution without affecting the drug structure as confirmed by IR and XRD. No considerable advantage was seen of increasing solvent ratio with drug.

Keywords: candesartan cilexetil, improved dissolution, solubility, liquisolid

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Authors: Shuofeng Yuan, Bojian Zheng

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Assembly of the heterotrimeric polymerase complex of influenza virus from the individual subunits PB1, PA, and PB2 is a prerequisite for viral replication, in which the interaction between the N-terminal of PB1 (PB1N) and the C terminal of PA (PAC) may be a desired target for antiviral development. In this study, we first compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (ELISA) and fluorescence polarization (FP) assay. Among the two, ELISA was demonstrated to own broader dynamic range so that it was used for screening inhibitors, which blocked PA and PB1 interaction. Several binding inhibitors of PAC-PB1N were identified and subsequently tested for the antiviral efficacy. Apparently, 3-(2-chlorophenyl)-6-ethyl-7-methyl[1,2,4]triazolo[4,3-a]pyrimidin-5-ol, designated ANA-1, was found to be a strong inhibitor of PAC-PB1N interaction and act as a potent antiviral agent against the infections of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 subtypes, in cell cultures. Intranasal administration of ANA-1 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted that ANA-1 bound to an allosteric site of PAC, which would cause conformational changes thereby disrupting the PAC-PB1N interaction. Overall, our study has identified a novel compound with potential to be developed as an anti-influenza drug.

Keywords: influenza, antiviral, viral polymerase, compounds

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Authors: Theresa Campbell, Camille Bowen-Forbes, William Aalbersberg

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Differences in the sensory properties of two subtly distinct varieties of Rubus rosifolius lead to the examination of their anthocyanin, essential oil and polyphenol profiles. In both cases, notable differences were identified. Pelargonidin-3-rhutinoside (17.2 mg/100 g FW) and Cyanidin-3-glucoside (66.2 mg/100g FW) proved to be the dominant anthocyanins in the red and wine red varieties respectively. Linalool and terpineol were the major constituents of the essential oil from the red variety; however, those of the wine red variety are unidentified. In regard to phenolic compounds, caffeic acid and quercetin were in a higher concentration in the red variety (1.85 and 0.73 mg/100g FW respectively, compared to 1.22 and 0.34 mg/100g FW respectively in the wine red fruits); while ellagic acid and ferulic acid were of a higher concentration in the wine red variety (0.92 and 0.84mg/100g FW respectively, compared to 0.15 and 0.48 mg/100g FW respectively in the red variety). The methanol extract of both fruit varieties showed great antioxidant activity. Analysis of the antimicrobial activity of the fruit extracts against the growth of drug resistant pathogens revealed that they are active against methicillin resistant S. aureus (MRSA), rifampicin resistant S. aureus (RRSA), wild-type S. aureus (WTSA) and vancomycin-resistant Enterococcus faecium (VREF). Activity was also reported against several food-borne pathogens including two strains of E. coli, L. monocytogenes and Enterobacter aerogenes. The cytotoxicity of the various extracts was assessed and the essential oil extracts exhibited superior activity. The phenolic composition and biological activity of the fruits indicate that their consumption is beneficial to health and also that their incorporation into functional foods and nutraceuticals should be considered.

Keywords: phytochemicals, antimicrobial, cytotoxic, Rubus rosifolius

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Authors: Patcharakamon Nooeaid, Piyachat Chuysrinuan

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Electrospun natural polymers-based nanofibers are one of the most interesting materials used in tissue engineering and drug delivery applications. Bead-on-string nanofibers have gained considerable interest for sustained drug release. Vancomycin was used as the model drug and sodium alginate (SA)/soy protein isolated (SPI) as the polymer blend to fabricate the bead-on-string nanofibers by aqueous-based electrospinning. The bead-on-string SA/SPI nanofibers were successfully fabricated by the addition of poly(ethylene oxide) (PEO) as a co-blending polymer. SA-PEO with mass ratio of 70/30 showed the best spinnability with continuous nanofibers without the occurrence of beads. Bead structure formed with the addition of SPI and bead number increased with increasing SPI content. The electrospinning of 80/20 SA-PEO/SPI was obtained as a great promising bead-on-string nanofibers for drug loading, while the solution of 50/50 was not able to obtain continuous fibers. In vitro release tests showed that a more sustainable release profile up to 14 days with less initial burst release on day 1 could be obtained from the bead-on-string fibers than from smooth fibers with uniform diameter. In addition, vancomycin-loaded beaded fibers inhibited the growth of Staphylococcus aureus (S. aureus) bacteria. Therefore, the SA-PEO/SPI nanofibers showed the potential to be used as biomaterials for tissue engineering and drug delivery.

Keywords: bead-on-string fibers, electrospinning, drug delivery, tissue engineering

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