Search results for: extensively drug resistant (XDR)-TB

Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Aakanchha Jain, D. V. Kohli

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Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of water with a microstructure that provides unique properties of practical interest. Cubosomes encapsulating Fluconazole were prepared by emulsification method and characterized for particle size, entrapment efficiency. The cubosomes prepared were 257.2±2.94 nm in size with drug entrapment efficiency of 66.2±2.69%. The optimized formulation characterized for shape and surface morphology by TEM and SEM analysis. SEM photograph showed the smooth surface of optimized cubosomes and TEM photograph revealed square somewhat circular intact shapes of cubosomes. MIC was determined by XTT based method and antifungal activity was determined in vitro. The cumulative percentage of Fnz from cubosomes permeated via dialysis membrane (MWCO 12-14 KD) showed a percent cumulative drug release of 76.86% while Fnz solution showed release up to 91.04% in 24 hours in PBS (pH 6.5)(p < 0.005).

Keywords: Candids albicans, cubosomes, fluconazole, topical delivery

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Authors: Ganesh B. Shinde, Vijaya B. Musande

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Cotton crop identification based on the timely information has significant advantage to the different implications of food, economic and environment. Due to the significant advantages, the accurate detection of cotton crop regions using supervised learning procedure is challenging problem in remote sensing. Here, classifiers on the direct image are played a major role but the results are not much satisfactorily. In order to further improve the effectiveness, variety of vegetation indices are proposed in the literature. But, recently, the major challenge is to find the better vegetation indices for the cotton crop identification through the proposed methodology. Accordingly, fuzzy c-means clustering is combined with neural network algorithm, trained by Levenberg-Marquardt for cotton crop classification. To experiment the proposed method, five LISS-III satellite images was taken and the experimentation was done with six vegetation indices such as Simple Ratio, Normalized Difference Vegetation Index, Enhanced Vegetation Index, Green Atmospherically Resistant Vegetation Index, Wide-Dynamic Range Vegetation Index, Green Chlorophyll Index. Along with these indices, Green Leaf Area Index is also considered for investigation. From the research outcome, Green Atmospherically Resistant Vegetation Index outperformed with all other indices by reaching the average accuracy value of 95.21%.

Keywords: Fuzzy C-Means clustering (FCM), neural network, Levenberg-Marquardt (LM) algorithm, vegetation indices

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Authors: Jasna Čanadanović-Brunet, Lidija Jevrić, Gordana Ćetković, Vesna Tumbas Šaponjac, Jelena Vulić, Slađana Stajčić

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Wheat contains high amount of nutrients such as dietary fiber, resistant starch, vitamins, minerals and microconstituents, which are building blocks of body tissues, but also help in the prevention of diseases such as cardiovascular disease, cancer and diabetes. Sprouting enhances the nutritional value of whole wheat through biosynthesis of tocopherols, polyphenols and other valuable phytochemicals. Since the nutritional and sensory benefits of germination have been extensively documented, using of sprouted grains in food formulations is becoming a trend in healthy foods. The present work addressed the possibility of using freeze-dried sprouted wheat powder, obtained from spelt-wheat cv. ‘Nirvana’ (Triticum spelta L.) and winter wheat cv. ‘Simonida’ (Triticum aestivum L. ssp. vulgare var. lutescens), as a source of phytochemicals, to improve the functional status of the consumer. The phytochemicals' content (total polyphenols, flavonoids, chlorophylls and carotenoids) and biological activities (antioxidant activity on DPPH radicals and antiinflammatory activity) of sprouted wheat powders were assessed spectrophotometrically. The content of flavonoids (216.52 mg RE/100 g), carotenoids (22.84 mg β-carotene/100 g) and chlorophylls (131.23 mg/100 g), as well as antiinflammatory activity (EC50=3.70 mg/ml) was found to be higher in sprouted spelt-wheat powder, while total polyphenols (607.21 mg GAE/100 g) and antioxidant activity on DDPPH radicals (EC50=0.27 mmol TE/100 g) was found to be higher in sprouted winter wheat powders. Simulation of gastro-intestinal digestion of sprouted wheat powders clearly shows that intestinal digestion caused a higher release of polyphenols than gastric digestion for both samples, which indicates their higher bioavailability in the colon. The results of the current study have shown that wheat sprouts can provide a high content of phytochemicals and considerable bioactivities. Moreover, data reported show that they contain a unique pattern of bioactive molecules, which make these cereal sprouts attractive functional foods for a health-promoting diet.

Keywords: wheat, sprouts, phytochemicals, bioactivity

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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Authors: Mehrnaz Mostafavi

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Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

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The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

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Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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Authors: Carol Yue-En Ong, Angelina Hui-Min Tan, Quan Liu, Paul Chi-Lui Ho

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A public general hospital in Singapore has recently implemented an automated unit-dose machine in their inpatient dispensary, Swisslog, with the objective of reducing human error and improving patient safety. However, a concern in stability arises as tablets are removed from their original packaging (bottled loose tablets/capsules) and are repackaged into individual, clear plastic wrappers as unit doses in the system. Drugs that are light-sensitive and hygroscopic would be more susceptible to degradation as the wrapper does not offer full protection. Hence, this study was carried out to study the stability of haloperidol tablets and phenytoin capsules that are light-sensitive and hygroscopic respectively. Validated HPLC-UV assays were first established for quantification of these two compounds. The medications involved were put in the Swisslog and sampled every week for one month. The collected data was analysed and showed no degradation over time. This study also explored an alternative approach for drug stability determination-Raman spectroscopy. The advantage of Raman spectroscopy is its high time efficiency and non-destructive nature. The results suggest that drug degradation can indeed be detected using Raman microscopy, but further research is needed to establish this approach for quantification or qualification of compounds. NanoRam®, a portable Raman spectrocope was also used alongside Raman microscopy but was unsuccessful in detecting degradation in this study.

Keywords: drug stability, haloperidol, HPLC, phenytoin, raman spectroscopy, Swisslog

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Authors: Nabil A. Albaser

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Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.

Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde

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Authors: Margita Čanigová, Jana Račková, Miroslav Kročko, Viera Ducková, Vladimíra Kňazovická

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The aim of the study was to test the milk samples in terms of enterococci presence and their counts. Tested samples were as follows: raw cow milk, raw cow milk stored at 10°C for 16 hours and milk pasteurised at 72°C for 15 seconds. The typical colonies were isolated randomly and identified by classical biochemical test - EN-COCCUS test (Lachema, CR) and by PCR. Isolated strains were tested in terms of antibiotic resistance by well diffusion method. Examined antibiotics were: vancomycin (30 μg/disc), gentamicin (120 μg/disc), erythromycin (15 μg/disc), teicoplanine (30 μg/disc), ampicillin (10 μg/disc) and tetracycline (30 μg/disc). Average value of enterococci counts in raw milk cistern samples (n=30) was 8.25 ± 1.37 ×103 CFU/cm3. Storage tank milk samples (n=30) showed an increase (P > 0.05) and average value was 9.16 ± 1.49 × 103 CFU/cm3. Occurrence of enterococci in pasteurized milk (n=30) was sporadic and their counts were mostly below 10 CFU/cm3. Overall, 96 enterococci strains were isolated. In samples of raw cow milk and stored raw cow milk, Enterococcus faecalis was a dominant species (58.1% and 71.7%, respectively), followed by E. faecium (16.3% and 0%, respectively). Enterococcus mundtii, E. casseliflavus, E. durans and E. gallinarum were isolated, too. Resistances to ampicillin, erythromycin, gentamicin, tetracycline and vancomycin were found in 7.29%, 3.13%, 4.00%, 13.54% and 10.42% of isolated enterococci strains, respectively. Resistance to teicoplanine was not found in any isolated strain. All Vancomycin-Resistant Enterococci (VRE) belonged to E. faecalis. Obtained results confirmed that raw milk is a potential risk of enterococci resistant to antibiotics transmission into the food chain.

Keywords: antibiotic resistance, enterococci, milk, biosystems engineering

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Chang-Hwan Oh, Young-Jong Lee

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In April, 2015, the Ministry of Food and Drug Safety’s announcement that only 10 of the 207 products that list Cynanchum Wilfordii Radix among their ingredients were confirmed to actually contain “iyeobupiso” the counterfeit version of the “baeksuo” raised a fog to consumers who purchased health/functional foods supposedly containing the herbal medicinal material, “baeksuo” in Korean. Baeksuo is the main ingredient of the product “EstroG-100” that contain Phlomis umbrosa and Angelica gigas too (NaturalEndoTech, S.Korea). The hot water extract of the herbal medicinal materials (HMM) was approved as a product specific Health/Functional Food (HFF) having a helpful function to women reaching menopause by Korea Food & Drug Administration (Ministry of Food & Drug Safety at present). The origin of “baeksuo” is the root of Cynanchum wilfordii Hemsley in Korea (But “iyeobupiso, the root of Cynanchum auriculatum Royle ex Wight is considered as the origin of “baeksuo” in China). In Korea, about 116 HMMs are listed as the food materials in Korea Food Code among the total 187 HMMs could be used for food and medicine purpose simultaneously. But there are some chances of the HMMs (shared use for food and medicine purpose) could be misused by the part and HMMs not permitted for HFF such as the “baeksuo” case. In this study, some of HMMs (shared use for food and medicine purpose) are examined to alleviate the misuse chance of HMMs for HFFs in Korea. For the purpose of this study, the origin, shape, edible parts, efficacy and the side effects of the similar HMMs to be misused for HFF are investigated.

Keywords: herbal medicinal materials, healthy/functional foods, misuse, shared use

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Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Georgia M. Michailidou, Nina-Maria S. Ainali, Eleftheria C. Xanthopoulou, Dimitrios N. Bikiaris

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Polysaccharides are polymeric materials derived from nature. They are extensively used in pharmaceutical technology due to their low cost, their ready availability and their low toxicity. Chitosan is the product derived from the deacetylation of chitin usually obtained from arthropods. It is a linear polysaccharide which is composed of repeated units of N-deacetylated amino groups and some N-acetylated groups residues. Due to its excellent biological properties, it is an attractive natural polymer. It is biocompatible with low toxicity and complete biodegradability. Although it has excellent properties, the chemical modification of its structure results in new derivatives with ameliorated and more improved properties compared to the initial polymer. This is the exact purpose of the present study in which chitosan was modified with three different monomers, namely trans-aconitic acid, succinic anhydride and 2-hydroxyethyl acrylate. In chitosan’s modification with trans aconitic acid, EDC was utilized as an activator of the carboxylic groups of the monomer, and then a coupling reaction with the amino groups took place. Succinic anhydride reacted with chitosan through a ring opening reaction while 2-hydroxyethyl acrylate reacted through the addition of chitosan’s amino group to the double bond of the monomer. Through FTIR and NMR measurements the success of each reaction was confirmed, and the new structures of the derivatives were verified. X-ray diffraction was utilized in order to examine the effect of the modifications in chitosan’s crystallinity. Finally, swelling tests were conducted in order to assess the improved ability of the new polymeric materials to absorb water. Our results support the successful modification of chitosan’s macromolecular chains in all three reactions. Furthermore, the new derivatives appear to be amorphous concerning their crystallinity and have great ability in absorbing water.

Keywords: chitosan, derivatives, modification, polysaccharide

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Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

Abstract:

The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Seyran Naghdi

Abstract:

Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: Parisa Shirzadeh

Abstract:

Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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Authors: Recep Keşli, Hayriye Tokay, Cengiz Demir, İsmail Ceyhan

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Objective: In many countries, tuberculosis (TB) is still one of the most important diseases. Tuberculosis is among top 10 causes of death worldwide. The early diagnosis of active tuberculosis still depends on the presence of acid resistant bacilli (ARB) in stained smears. In this study, we aimed to investigate the diagnostic performances of Erlich Ziehl Neelsen (EZN), Kinyoun and two different fluorescent stains. Methods: The specimens were obtained from the patients who applied to Chest Diseases Departments of Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, and Afyon Kocatepe University, ANS Research and Practice Hospital. The study was carried out in the Medical Microbiology Laboratory, School of Medicine, Afyon Kocatepe University. All the non-sterile specimens were homogenized and decontaminated according to the EUCAST instructions. Samples were inoculated onto the Löwenstein-Jensen agars (bio-Merieux Marcy l'Etoile, France) and then incubated at 37˚C, for 40 days. Four smears were prepared from each specimen. Slides were stained with commercial EZN (BD, Sparks, USA), Kinyoun (SALUBRIS Istanbul, Turkey), Auramine (SALUBRIS Istanbul, Turkey) and Rhodamine (SALUBRIS Istanbul, Turkey) kit. While EZN and Kinyoun stainings were examined by light microscope, Auramine and Rhodamine slides were examined by fluorescence microscopy. Results: A total of 158 respiratory system samples (sputum, broncho alveolar lavage fluid…etc) were enrolled into the study. A hundred and two of the samples that processed were found as culture positive. The sensitivity, specificity, positive predictive, and negative predictive values were detected as 100%, 67.5%, 73.5%, and 100% for EZN, 100%, 70.9%, 77.4%, and 100% for Kinyoun, 100%,77.8%, 84.3%, 100% for Auramine, and 100%, 80% , 86.3%, and 100% for Rhodamine respectively. Conclusions: According to our study auramine and rhodamine staining methods showed the best diagnostic performance among the four investigated staining methods. In conclusion, the fluorochrome staining method may be accepted as the most reliable, rapid and useful method for diagnosis of the mycobacterial infections truly.

Keywords: acid resistant bacilli (ARB), auramine, Ehrlich-Ziehl-Neelsen (EZN), Kinyoun, Rhodamine

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Authors: Zohra Benfodda, Valentin Duvauchelle, Chaimae Majdi, David Bénimélis, Catherine Dunyach-Remy, Patrick Meffre

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New antibiotics are necessary to treat microbial pathogens, especially ESKAPE pathogens that are becoming increasingly resistant to available treatment. Despite the medical need, the number of newly approved drugs continues to decline. The majority of antibiotics under clinical development are natural products or derivatives thereof. 43 juglone/naphthazarin derivatives were synthesized using Minisci-type direct C–H alkylation and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA. Different compounds of the synthesized series showed promising activity against clinical and reference MSSA (MIC: 1–8 μg/ml) and good efficacy against clinical MRSA (MIC: 2–8 μg/ml) strains. The synergistic effects of active compounds were evaluated with reference antibiotics (vancomycin and cloxacillin), and it was found that the antibiotic combination with those active compounds efficiently enhanced the antimicrobial activity and consequently the MIC values of reference antibiotics were lowered up to 1/16th of the original MIC. These synthesized compounds did not present hemolytic activity on sheep red blood cells. In addition to the in silico prediction of ADME profile parameter which is promising and encouraging for further development.

Keywords: juglone, naphthazarin, antibacterial, clinical MRSA, synergistic studies, MIC determination

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Authors: Ajmal Khan Kassi, Humayun Javed, Tariq Mukhtar

Abstract:

The research was conducted to screen out resistance and susceptibility of okra varieties against Helicoverpa armigera under field conditions 2016. In this experiment, the different management practices viz. release Trichogramma chilonis, hoeing, and weeding, clipping, and lufenuron were tested individually and with all possible combinations for the controlling of American bollworm at 3 diverse localities viz. University research farm Koont, National Agriculture Research Centre (NARC) and farmer field Taxila by using resistant variety Arka Anamika. All the treatment combinations regarding damage of shoot and fruit showed significant results. The minimum fruit infestation, i.e., 3.20% and 3.58% was recorded with combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in two different localities. The minimum shoot infestation, i.e., 7.18%, 7.08%, and 6.85% was also observed with (T. chilonis + hoeing + weeding + lufenuron) combined treatment at all three different localities. The above-combined treatment (T. chilonis + hoeing + weeding + lufenuron) also resulted in maximum yield at NARC and Taxila, i.e., 57.67 and 62.66 q/ha respectively. On the basis of combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in three different localities, Arka Anamika variety proved to be comparatively resistant against H. armigera. So this variety is recommended for the cultivation in Pothwar region to get maximum yield and minimum losses against H. armigera.

Keywords: okra, screening, combine treatment, Helicoverpa armigera

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Authors: Hind Bouami, Patrick Millot

Abstract:

Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.

Keywords: Automated drug delivery systems, Hospitals, Human-centered automated system, Risk management

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Osama K. Abou-Zied, Saba A. Sulaiman

Abstract:

We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.

Keywords: gold nanoparticles, human serum albumin, fluorescein, femtosecond transient absorption

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Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

Abstract:

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

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