Excellence in Research and Innovation for Humanity

International Science Index

Commenced in January 1999 Frequency: Monthly Edition: International Abstract Count: 46035

Pharmacological and Pharmaceutical Sciences

847
80531
Differential Effects of Parity, Stress and Fluoxetine Treatment on Locomotor Activity and Swimming Behavior in Rats
Abstract:
Peripartum period is a time where women are vulnerable to depression, and stress may further increase the risk of its occurrence. Use of selective serotonin reuptake inhibitors (SSRI) in the treatment of postpartum depression is a common practice. Comparison of antidepressant treatment, however, is rarely studied between gestated and nulliparous animals exposed to stress. This study was aimed to investigate the effect of parity and stress, as well as fluoxetine (an SSRI) treatment after stress exposure on the behavior of rats. Gestating and nulliparous Sprague Dawley rats were either subjected to chronic stressors or left undisturbed throughout the gestation period. After parturition, all stressors were stopped and some of the stressed rats were treated with fluoxetine (10mg/kg). Hence, the final groups formed were: 1. Non-stressed nulliparous rats, 2. Non-stressed dams, 3. Stressed nulliparous rats, 4. Stressed dams, 5. Fluoxetine-treated stressed nulliparous rats, and 6. Fluoxetine-treated stressed dams. Rats were tested in open field test (OFT), novel object recognition test (NOR) and forced swim test (FST) after weaning of pups. Gestational stress significantly reduced the locomotor activity of rats in OFT (p< 0.05), while fluoxetine significantly increased the activity in nulliparous rats (p< 0.001) but not the dams. While no differences were observed in NOR, stress and parity inhibited the rats from performing swimming behavior in FST. However, climbing and immobile behaviors in FST were found to have no significant differences, although there is a tendency of effect of treatment for immobility parameter (p=0.06) where fluoxetine-treated stressed dams were being the least immobile. In conclusion, the effects of parity and stress, as well as fluoxetine treatment, depended on the type of behavioral test performed.
846
80502
Impact of Fluid Flow Patterns on Metastable Zone Width in Dual Radial Impeller Crystallizer at Different Impeller Spacings
Abstract:
Conducting crystallization in an agitated vessel requires a proper selection of mixing parameters that would result in a production of crystals of specific properties. In dual impeller systems, which are characterized by a more complex hydrodynamics due to the possible fluid flow interactions, revealing a clear link between mixing parameters and crystallization kinetics is still an open issue. The aim of this work is to establish this connection by investigating how fluid flow patterns, generated by two impellers mounted on the same shaft, reflect on metastable zone width of borax decahydrate, one of the most important parameters of the crystallization process. Investigation was carried out in a 15 dm3 bench scale batch cooling crystallizer with an aspect ratio (H/T) equal to 1.3. For this reason, two radial straight blade turbines (4-SBT), placed at different impeller spacings, were used for agitation. Experiments were conducted at the state of complete suspension (N/NJS=1). During the process of an unseeded batch cooling crystallization, solution temperature and supersaturation were continuously monitored potentiometrically what enabled a determination of the metastable zone width. Hydrodynamic conditions in this type of crystallizer were analyzed in detail. This was done firstly by measuring the mixing time required to attain the wanted level of system homogeneity. Secondly, fluid flow patterns generated in a described dual impeller agitated vessel were both photographed and simulated by VisiMix Turbulent software. Comparison of these two visualization methods was performed. Experimentally obtained results showed that metastable zone width is definitely affected by the hydrodynamics in the crystallizer, achieved at different impeller spacings. This means that this crystallization parameter can be controlled not only by adjusting the saturation temperature or cooling rate, as is most frequently done, but also by choosing a suitable impeller spacing that will result in a formation of crystals of wanted size distribution.
845
80319
Formulation and In Vitro Evaluation of Transdermal Delivery of Articaine
Abstract:
The objective of this study is to formulate different topical preparations containing articaine and to investigate their permeation through goat skin. Initially, articaine and its hydrochloride salt were compared for in vitro permeation using Franz cell model. Goat skin samples were collected after euthanizing male goat kids purchased from the dairy goat farmers. Subcutaneous fat was removed and the skin was mounted on the donor chamber (orifice area 1.00 cm²) and drugs were applied onto the epidermis. Phosphate buffer saline (pH 7.4) was used to maintain sink condition in the receptor chamber (8 ml) of the Franz cell. Samples (0.4 ml) were collected at various intervals over 24 hours after each sampling equal volume of PBS was replaced in the receptor chamber. Articaine in the collected samples were quantified using LC/MS. The results suggested that articaine free base permeates better than its hydrochloride salt through goat skin. This study results support the fact that local anesthetics in its base form are lipophilic and thus penetrates faster through cell membranes than their salts. Later, articaine free base was formulated either using ethanol and octyl salicylate or dimethyl sulfoxide (DMSO) as penetration enhancers and was compared for in vitro permeation. The transdermal flux of articaine in the formulation containing DMSO was approximately 3.8 times higher than that of the formulation containing ethanol and octyl salicylate. Further studies to evaluate the local anesthetic efficacy of the topical formulation containing articaine for dermal anesthesia in animals have been planned.
844
79952
Quality Control Parameters and Pharmacological Aspects of Less Known Medicinal Plant of India: Plumeria pudica Linn.
Abstract:
Plumeria pudica Linn. Family Apocynaceae commonly known as Nag Chmapa is grown wildly in many parts of India. The plant is medium size shrub, grown up to height of 5-10 feet, evergreen with white flowers. In traditional system of medicine, the plant is widely used in the treatment of worms, infection, inflammation, etc. So, far no any systematic and documented study was done to revealed quality control parameters and pharmacological aspect of the selected plant species, therefore, the attempt was made in present investigation to reveal the same. The parameters such as Ash value, FOM, LOD, SI, etc. were studied using various coarsely dried plant materials of the species. Analgesic, anti-inflammatory, anthelmentic and anti-microbial activity of various extract was investigated and reported in present work.
843
79762
Cardiotrophin-1 and Leptin in Male Patients with Obstructive Sleep Apnea Syndrome
Abstract:
Elevated serum Cardiotrophin-1 (CT-1) and leptin levels are important risk factors for cardiovascular diseases (CVDs).Obstructive sleep apnea syndrome (OSAS) has been reported to increase the risk of CVDs, too. The aim of this study was to evaluate the concentrations of serum CT-1 and leptin in these patients and whether their possible association with the disease severity. Fifty newly diagnosed patients with OSAS and thirty nonapneic snoring subjects were participated in this study.The mean ages of patients and control groups were 47.40±13.30 and 43.23±10.50 years, respectively (P=0.128). Fasting serum triglyseride, total cholesterol, LDL and HDL cholesterol, also CT-1 and leptin levels were evaluated. A significant difference was found in the serum CT-1 and leptin levels between the patients and the controls: serum median CT-1 levels in patients and control groups, respectively, were 19.47 and 8.23 pg/mL (P< 0.001) and leptin levels were 2.07 and 1.29 ng/mL (P< 0.001). In severe patients group (n=39), serum median CT-1 level was found statistically significantly higher than the median level in mild/moderate patients (n=11) group. Patients CT-1 concentrations were not associated with lipoprotein levels and there was no correlation between patients’ leptin and lipid profile parameters. Two risk factors for CVDs, CT-1 and leptin, have significantly elevated and they were associated with OSAS. Furthermore, CT-1 was associated with the severity of disease. We recommend the use of increased serum CT-1 and leptin concentrations as markers of the presence and severity of OSAS. They can be used as early markers in male OSAS patients without known CVDs.
842
79577
Chemical Composition, Antioxidant and Antimicrobial Activities of the Essential Oils of Different Pinus Species from Kosovo
Abstract:
Chemical profile, antioxidant and antimicrobial activity of total and fractionated essential oils (EOs) (F1 – hexane, F2 – hexane/diethyl ether, F3 – diethyl ether) derived from five Pinus species (Pinus heldreichii, P. peuce, P. mugo, Pinus nigra, P. sylvestris), were investigated. The hydrodistilled EOs and their chromatographic fractions (direct solid phase extraction, SPE) were analysed by GC-MS and 112 compounds separated and identified. The main constituents were α-pinene, β-pinene, D-limonene, β-caryophyllene, germacrene D, bornyl acetate and 3-carene. The antioxidant activities of total EOs were lower than those of the corresponding fractions, with F2 the strongest in all cases. EOs and fractions showed different degrees of antibacterial efficacy against different microbial pathogens (moderately strong antimicrobial activity against C. albicans and C. krusei ,while low or no activity against E. faecalis and E. coli strains). The detected inhibition zones and MICs for the EOs and fractions were in the range of 14 -35 mm and 0.125 - 1% (v/v), respectively. The components responsible for the antioxidant and antimicrobial activity were oxygenated monoterpenes and sesquiterpenes recovered in the polar EO fractions. These activities seem to be regulated by reciprocal interactions among the different subclasses of phytochemical species present in the EOs.
841
79572
Evaluation of Antimicrobial Activity of Phenolic Compounds Extracted from Jordanian Juglans regia L.
Abstract:
In this study we have examined of antimicrobial activity for unripe Juglan Regia phenolic extracts against a wide range of pathogenic microorganisms. Walnut (Juglans regia L.) is a member of Juglandaceae family used as a remedy in folk medicine. Leaves, barks, fruits and husk (peel) reported to harbor distinctive medical effect. In our study, we examined the anti-microbial effect against a set of gram positive and negative bacteria and even we have tested them against eukaryotic candida strains in a concentration gradual manner. Ethyl acetate extract of J. regia had the best antibacterial activity when compared with ciprofloxacin. The Minimum inhibition concentration for S. aureus, P. aerogenosa and S. epidermidis MIC was 0.85 mg/mL.
840
79491
Secondary Metabolites Identified from a Pseudoalteromonas rubra Bacterial Strain Isolated from a Fijian Marine Alga
Abstract:
The marine environment has continuously demonstrated to be a rich source of secondary metabolites and bioactive compounds that can address the many pharmaceutical problems facing mankind. The emergence of multidrug resistant pathogens has caused scientists to explore contemporary ways of combating these super bugs. A red-pigmented bacterial strain isolated from a marine alga collected in Fiji was identified to be Pseudoalteromonas rubra from 16s rRNA sequencing. This bacterial strain was cultured using a yeast-peptone media and incubated for five days. The ethyl acetate extract of this bacterium was subjected to chromatographic separation techniques such as vacuum liquid chromatography, flash chromatography, size exclusion chromatography and high-pressure liquid chromatography to yield the pure compound and a number of semi-pure fractions. The crude extract and subsequent purified fractions were analyzed by ultraviolet/visible spectroscopy and mass spectroscopy and was found to contain the compounds ivermectin, stenothricin, cyclo-L-pro-L-val, prodigiosin, mycophenolic acid, phenazine-1-carboxylic acid, eplerenone, staurosporine and pseudoalteromone A. The structure of the pure compound, pseudoalteromone A, was elucidated using NMR 1H, 13C, 1H-1H COSY, HSQC and HMBC spectroscopic data.
839
79050
Antibiotic Potential of Bioactive Compounds from a Marine Streptomyces Isolated from South Pacific Sediments
Abstract:
Two bioactive compounds namely Vulgamycin (also known as enterocin A) and 5-deoxyenterocin were purified from a marine bacterial strain 1903. Strain 1903 was isolated from marine sediments collected from the Solomon Islands. Morphological features of strain 1903 showed that it belongs to the genus Streptomyces. The two secondary metabolites were extracted using EtOAc and purified by chromatographic methods using EtOAc and hexane solvents. Mass spectrum and NMR data of pure compounds were used to elucidate the chemical structures. In this study, results showed that both compounds were strongly active against Wild Type Staphylococcus aureus (WTSA) (MIC < 1 µg/mL) and in Brine shrimp assays (BSA) (MIC < 1 µg/mL). 5-deoxyenterocin was also active against Rifamycin resistant Staphylococcus aureus (RRSA) (MIC, 250 µg/mL) while vulgamycin showed bioactivity against Methicillin resistant Staphylococcus aureus (MRSA) (MIC 250 µg/mL). To the best of our knowledge, this is the first study that showed the bio-activity of 5-deoxyenterocin. This is also the first time that Vulgamycin has been reported to be active in a BSA. There has not been any mechanism of action studies for these two compounds against pathogens. This warrants further studies on their mechanism of action against microbial pathogens.
838
78962
The Impact of Psychopathology Course on Students' Attitudes towards Mental Illness
Abstract:
Background: Negative attitudes towards the mentally ill are widespread and a course for concern as they have a detrimental impact on individuals affected by mental illness. A possible avenue for changing attitudes towards mental illness is through mental health literacy. In a college or university setting, an abnormal psychology course may be introduced in an attempt to change student’s attitudes towards the mentally ill. Objective: To determine if and how students’ attitudes towards the mentally ill change as a result of taking a course in abnormal psychology. Methods: Twenty nine (29) students were recruited from an abnormal psychology class at the University of Botswana. Attitude Scale for Mental Illness (ASMI) questionnaire was administered to participants at the beginning and end of the semester. SPSS was employed to analyze data. Pooled means were used to determine whether the student’s attitudes towards mental illness were negative or positive. A mean of 2.5 translated to negative attitude for both total attitude and attitudes in different domains of the scale. Paired sample t-test was then used to assess whether any changes noted in attitudes were statistically significant or not. Statistical significance was assumed at p < 0.05. Results: Students’ general attitude towards mental illness remained positive although the pooled mean value increased from 2.08 to 2.24. The change was not statistically significant. In relation to different sub scales, the values of the pooled means for all the sub scales showed an increase although the changes were not statistically significant except for the Stereotyping sub scale (p = 0.031). The stereotyping domain reflected a statistically significant change in student’s attitude from positive attitude to negative (X² = 2.06 to X² = 2.55). For the pessimistic prediction domain, students consistently showed a negative attitude (X² = 3.34 to X² = 3.55). The other 4 domains indicated that students had positive attitude toward mentally ill throughout. Discussion: Abnormal psychology students have a positive attitude towards the mentally ill generally. This could be attributed to the fact that all students in the abnormal psychology course are majoring in psychology and research has shown that interest in psychology can affect one’s attitude towards mental illness. The students continuously held the view that people with mental illness are unlikely to improve as evidenced by a high score for Pessimistic prediction domain for both pre and post-test. Students initially had no stereotyping attitude towards the mentally ill, but at the end of the course, they were of the opinion that people with mental illness can be defined in a certain behavioural pattern and mental ability. This results could be an indication that students have learnt well how to differentiate abnormal from normal behaviour not necessarily that students had developed a negative attitude. Conclusion: A course in abnormal psychology does have an impact on the students’ attitudes towards the mentally ill. The impact does not solely depend on knowledge of mental illness but also on several other factors such as contact with the mentally ill, interest in psychology, and teaching methods. However, it should be noted that sometimes improved knowledge in mental illness can be misunderstood for a negative attitude. For example, stereotyping attitudes may be a reflection of the ability to differentiate between abnormal and normal behaviour.
837
78941
Comparison of Extracellular miRNA from Different Lymphocyte Cell Lines and Isolation Methods
Abstract:
The development of a panel of differential gene expression signatures has been of interest in the field of biomarker discovery for radiation exposure. In the absence of the availability of exposed human subjects, lymphocyte cell lines have often been used as a surrogate to human whole blood, when performing ex vivo irradiation studies. The extent of variation between different lymphocyte cell lines is currently unclear, especially with regard to the expression of extracellular miRNA. This study compares the expression profile of extracellular miRNA isolated from different lymphocyte cell lines. It also compares the profile of miRNA obtained when different exosome isolation kits are used. Lymphocyte cell lines were created using lymphocytes isolated from healthy adult males of similar racial descent (Chinese American and Chinese Singaporean) and immortalised with Epstein-Barr virus. The cell lines were cultured in exosome-free cell culture media for 72h and the cell culture supernatant was removed for exosome isolation. Two exosome isolation kits were used. Total exosome isolation reagent (TEIR, ThermoFisher) is a polyethylene glycol (PEG)-based exosome precipitation kit, while ExoSpin (ES, Cell Guidance Systems) is a PEG-based exosome precipitation kit that includes an additional size exclusion chromatography step. miRNA from the isolated exosomes were isolated using miRNEASY minikit (Qiagen) and analysed using nCounter miRNA assay (Nanostring). Principal component analysis (PCA) results suggested that the overall extracellular miRNA expression profile differed between the lymphocyte cell line originating from the Chinese American donor and the cell line originating from the Chinese Singaporean donor. As the gender, age and racial origins of both donors are similar, this may suggest that there are other genetic or epigenetic differences that account for the variation in extracellular miRNA gene expression in lymphocyte cell lines. However, statistical analysis showed that only 3 miRNA genes had a fold difference > 2 at p < 0.05, suggesting that the differences may not be of that great a significance as to impact overall conclusions drawn from different cell lines. Subsequent analysis using cell lines from other donors will give further insight into the reproducibility of results when difference cell lines are used. PCA results also suggested that the method of exosome isolation impacted the expression profile. 107 miRNA had a fold difference > 2 at p < 0.05. This suggests that the inclusion of an additional size exclusion chromatography step altered the subset of the extracellular vesicles that were isolated. In conclusion, these results suggest that extracellular miRNA can be isolated and analysed from exosomes derived from lymphocyte cell lines. However, care must be taken in the choice of cell line and method of exosome isolation used.
836
78862
Establishing a Drug Discovery Platform to Progress Compounds into the Clinic
Authors:
Abstract:
The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.
835
78699
Preparation of Flurbiprofen Derivative for Enhanced Brain Penetration
Authors:
Abstract:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.
834
78580
Evaluation of Antimicrobial Use in a Tertiary Care Hospital by Using Specific Indicators: A Prospective, Observational Study
Abstract:
The discovery and usage of antimicrobial drugs is one of the most important and significant contributions to therapeutics in the 20th century. Apart from being very frequently used, they are often misused. The use and misuse of antimicrobial agents need to be evaluated since misuse of antimicrobials increases the risk of antimicrobial resistance while management and use of antimicrobials have clinical, economic, and environmental implications. This study was designed to assess the pattern of antimicrobial prescriptions, to identify the most common problems with antimicrobials prescription and to apply the various antimicrobial use indicators to check the appropriateness of antimicrobial prescribing pattern. A prospective, observational, hospital-based study was carried out at St. Philomena’s hospital located in Bangalore. Ethical committee clearance was obtained from the hospital before starting the study. The research student attended ward rounds on a daily basis and collected the cases which have been prescribed with antimicrobial agents. Both empirically prescribed antimicrobials, as well as the antimicrobials prescribed after culture sensitivity test, were included. Specified indicators were applied, and the collected data was analyzed. The results of this study indicate that women were slightly more vulnerable than men in developing infectious diseases who were majorly above 60 years of age. In this study, it was found that antibiotics were the most common type of antimicrobials prescribed among which cephalosporins and fluoroquinolones were the most common class of antibiotics used. Anti-fungals (Azoles) and antivirals (anti-influenza) were the next most common type of antimicrobials prescribed. It was also observed that lower respiratory tract infection was the most common infectious disease diagnosed in these patients among whom chronic obstructive pulmonary disease patients were completely treated according to the standard treatment guidelines while pneumonia patients were partially treated according to the standard treatment guidelines. In this study, various indicators were also applied to evaluate the use of antimicrobial agents, and it was found that the use of antimicrobials was not appropriate. The use of antimicrobials was evaluated, and it was found that there is a need to promote rational use of antimicrobials, as irrational use would lead to antimicrobial resistance.
833
78563
In vitro Determination of Carbonic Anhydrase Inhibition of the Flowers of Vanda Orchid, Vanda Tessellata Roxb. (1795) by Modified Colorimetric Maren T.H. (1960) Method
Abstract:
The orchid, Vanda tessellata was chosen by the researchers because of the presence of the constituents in the family Orchidaceae such as alkaloids, flavonoids and glycosides that might give an inhibition activity of the carbonic anhydrase enzyme. This study aimed to determine the in vitro inhibition of carbonic anhydrase of Vanda tessellata flower extract. With the use of modified colorimetric Maren T.H. (1960) method, the time in seconds each test solution changed its color after the rate of CO2 hydration were recorded. Two solvents were used: the semi-polar, 95% ethanol and the non-polar, dichloromethane solvents. The percent inhibition activity of carbonic anhydrase of the different concentrations of solvents ethanol (1%, 25% and 50%) and dichloromethane (1% and 10%) test solutions were determined. Results showed that the ethanol-based extract of Vanda tessellata in different concentrations showed an inhibitory effect while the dichloromethane-based extract of Vanda tessellata showed no inhibitory effect of carbonic anhydrase activity. For ethanol extract, the concentration with the highest activity was 50% followed by 25% which changed its color from red to yellow with an average time of 13.11 seconds and 11.57 seconds but 1% with an average time of 7.56 seconds did not exhibit an effect. The researchers recommend the isolation of the specific active constituents of Vanda tessellata that is responsible for the inhibitory effect of carbonic anhydrase enzyme. It is also recommended to utilize different blood types to observe different reactions to the inhibition of the carbonic anhydrase.
832
78553
Application of Liquid Chromatographic Method for the in vitro Determination of Gastric and Intestinal Stability of Pure Andrographolide in the Extract of Andrographis paniculata
Abstract:
Gastrointestinal stability of andrographolide was evaluated in vitro in simulated gastric (SGF) and intestinal (SIF) fluids using a validated HPLC-PDA method. The method was validated using a 5μm ThermoHypersil GOLD C18column (250 mm × 4.0 mm) and mobile phase consisting of water: acetonitrile; 70: 30 (v/v) delivered isocratically at a flow rate of 1 mL/min with UV detection at 228 nm. Andrographolide in pure form and extract Andrographis paniculata was incubated at 37°C in an incubator shaker in USP simulated gastric and intestinal fluids with and without enzymes. Systematic protocol as per FDA Guidance System was followed for stability study and samples were assayed at 0, 15, 30 and 60 min intervals for gastric and at 0, 15, 30, 60 min, 1, 2 and 3 h for intestinal stability study. Also, the stability study was performed up to 24 h to see the degradation pattern in SGF and SIF (with enzyme and without enzyme). The developed method was found to be accurate, precise and robust. Andrographolide was found to be stable in SGF (pH ∼ 1.2) for 1h and SIF (pH 6.8) up to 3 h. The relative difference (RD) of amount of drug added and found at all time points was found to be < 3%. The present study suggests that drug loss in the gastrointestinal tract takes place may be by membrane permeation rather than a degradation process.
831
78410
Iontophoretic Drug Transport: An Non-Invasive Transdermal Approach
Abstract:
There has been great interest in the field of Iontophoresis since few years due to its great applications in the field of controlled transdermal drug delivery system. It is an technique which is used to enhance the transdermal permeation of ionized high molecular weight molecules across the skin membrane especially Peptides & Proteins by the application of direct current of 1-4 mA for 20-40 minutes whereas chemical must be placed on electrodes with same charge. Iontophoresis enhanced the delivery of drug into the skin via pores like hair follicles, sweat gland ducts etc. rather than through stratum corneum. It has wide applications in the field of experimental, Therapeutic, Diagnostic, Dentistry etc. Medical science is using it to treat Hyperhidrosis (Excessive sweating) in hands and feet and to treat other ailments like hypertension, Migraine etc. Nowadays commercial transdermal iontophoretic patches are available in the market to treat different ailments. Researchers are keen to research in this field due to its vast applications and advantages.
830
78226
Investigation of Antioxidant and Hydroxyl Radical Scavenging Activity of Hibiscus Acetosella Extract
Abstract:
The aim of this study is investigation of antioxidant and hydroxyl radical scavenging activity of Hibiscus acetosella extract in gathering data for other researches and products development. Hibiscus acetosella were extracted with water, ethanol and methanol. The antioxidant activity were investigated by using ABTS assay and hydroxyl radical scavenging activity were investigated by using Fenton reaction. The results of this study showed Hibiscus acetosella extract had ability in antioxidant and hydroxyl radical scavenging which concentration is 10 mg/ml. The % inhibition of 10 mg/ml in antioxidant activity was 67.91% and hydroxyl radical scavenging activity was 64.12%. However, this study was not enough for using in products development which should study in other tests such as anti-inflammatory properties, cytotoxicity and pure compound analysis for increasing the efficacy of products from Hibiscus acetosella.
829
78188
Comparison Studies on the Computational Complexities of the EEDSA
Abstract:
The elliptic ElGamal digital signature algorithm (EEDSA) has been created based on the ElGamal public key cryptosystem (EPKC) and the algorithm of the digital signature (DSA), defined on the elliptic curves E, which was accepted in several (ANSI, IEEE, NIST and ISO) standards. The EEDSA has been improved based on replacing the computation of a scalar multiplication kP that is used the point addition and doubling on elliptic curve by using the integer sub-decomposition (ISD) method. A scalar k in kP , on the proposed EEDSA-ISD method, has been sub-decomposed by k ≡ k11+k12λ1+k21+k22 λ2 (mod n), where k11, k12 , k21 , k22 ∈ [−√n ,√n], λ1, λ2 ∈ [1, n − 1] with λ1≠±λ2 and n is a prime order of a point P which lies on E. The sub-scalars, namely k11, k12 , k21 , k22 are computed by solving the shortest vector problem in lattice. The scalar multiplications kP on the EEDSA-ISD method are computed by kP = k11+k12ψ1(P)+k21+k22 ψ2(P), where ψ1(P)=λ1P and ψ2(P)=λ2P are two efficiently computable endomorphisms of E defined over Fp. The proposed EEDSA-ISD algorithm is benefited from the fast computations in the ISD method which is depended on the sub-decomposition of the scalars in scalar multiplications. The EEDSA-ISD method also depended on speeding the computations of the efficiently computable endomorphisms ψi, for i = 1,2, of elliptic curve E in ISD method. This paper proposes another mechanism to improve the EEDSA based on using the Gallant, Lambert and Vanstone (GLV) method. On the proposed EEDSA-GLV method, a scalar k is decomposed as k ≡ k1+k2λ (mod n), with max{|k1|,|k2|} ≤ √n, λ ∈ [1,n-1]. The scalar multiplication kP has been computed by kP=k1P+k2ψ(P), where ψ(P) is an efficiently computable endomorphism of E defined over a prime field Fp. This work also sheds light mainly on the computational complexities of the EEDSA-GLV and EEDSA-ISD algorithms those will be determined by computing the cost of the operations. These operations include elliptic curve operations and finite field operations. As well as, this work compared these two proposed methods on the basis of the computational complexity of each technique in one cycle operation. Our experiments reveal that the EEDSA-ISD method is faster than EEDSA-GLV method. Thus, the EEDSA-ISD method considers as an efficient algorithm in compared with the original EEDSA and EEDSA-GLV for cryptographic usages
828
77906
Structure-Guided Optimization of Sulphonamide as Gamma–Secretase Inhibitors for the Treatment of Alzheimer’s Disease
Abstract:
In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.
827
77794
Monitoring the Pollution Status of the Goan Coast Using Genotoxicity Biomarkers in the Bivalve, Meretrix Ovum
Abstract:
The coast of Goa, India receives constant anthropogenic stress through its major rivers which carry mining rejects of iron and manganese ores from upstream mining sites and petroleum hydrocarbons from shipping and harbor-related activities which put the aquatic fauna such as bivalves at risk. The present study reports the pollution status of the Goan coast by the above xenobiotics employing genotoxicity studies. This is further supplemented by the quantification of total petroleum hydrocarbons (TPHs) and various trace metals (iron, manganese, copper, cadmium, and lead) in gills of the estuarine clam, Meretrix ovum as well as from the surrounding water and sediment, over a two-year sampling period, from January 2013 to December 2014. Bivalves were collected from a probable unpolluted site at Palolem and a probable polluted site at Vasco, based upon the anthropogenic activities at these sites. Genotoxicity was assessed in the gill cells using the comet assay and micronucleus test. The quantity of TPHs and trace metals present in gill tissue, water and sediments were analyzed using spectrofluorometry and atomic absorption spectrophotometry (AAS), respectively. The statistical significance of data was analyzed employing Student’s t-test. The relationship between DNA damage and pollutant concentrations was evaluated using multiple regression analysis. Significant DNA damage was observed in the bivalves collected from Vasco which is a region of high industrial activity. Concentrations of TPHs and trace metals (iron, manganese, and cadmium) were also found to be significantly high in gills of the bivalves collected from Vasco compared to those collected from Palolem. Further, the concentrations of these pollutants were also found to be significantly high in the water and sediments at Vasco compared to that of Palolem. This may be due to the lack of industrial activity at Palolem. A high positive correlation was observed between the pollutant levels and DNA damage in the bivalves collected from Vasco suggesting the genotoxic nature of these pollutants. Further, M. ovum can be used as a bioindicator species for monitoring the level of pollution of the estuarine/coastal regions by TPHs and trace metals.
826
77700
Antibacterial Activity of Silver Nanoparticles of Extract of Leaf of Nauclea latifolia (Sm.) against Some Selected Clinical Isolates
Abstract:
Nauclea latifolia is one of the medicinal plants used in traditional Nigerian medicine in the treatment of various diseases such as fever, toothaches, malaria, diarrhea among several other conditions. Nauclea latifolia leaf extract acts as a capping and reducing agent in the formation of silver nanoparticles. Silver nanoparticles (AgNPs) were synthesized using a combination of aqueous extract of Nauclea latifolia and 1mM of silver nitrate (AgNO₃) solution to obtain concentrations of 100mg/ml-400mg/ml. Characterization of the particles was done by UV-Vis spectroscopy and Fourier transform infrared (FTIR). In this study, aqueous as well as ethanolic extract of leaf of Nauclea latifolia were investigated for antibacterial activity using the standard agar well diffusion technique against three clinical isolates (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). The Minimum Inhibitory Concentration (MIC) was achieved by microbroth dilution method and Minimum Bactericidal Concentration (MBC) was also determined by plate assay. Characterization by UV-visible spectrometry revealed peak absorbance of 0.463 at 450.0nm, while FTIR showed the presence of two functional groups. At 400mg/ml, the highest inhibitory activities were observed with S.aureus and E.coli with zones of inhibition measuring 20mm and 18mm respectively. The MIC was obtained at 400mg/ml while MBC was at a higher concentration. The data from this study indicate the potential of silver nanoparticle of Nauclea latifolia as a suitable alternative antibacterial agent for incorporation into orthodox medicine in health care delivery in Nigeria.
825
77684
Proliferative Effect of Some Calcium Channel Blockers on the Human Embryonic Kidney Cell Line
Abstract:
Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p< 0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.
824
77548
Curcumin and Its Analogues: Potent Natural Antibacterial Compounds against Staphylococcus aureus
Abstract:
Staphylococcus aureus is the most pathogenic of all staphylococci, a major cause of nosocomial infections, and known for acquiring resistance towards various commonly used antibiotics. Due to the widespread use of synthetic drugs, clinicians are now facing a serious threat in healthcare. The increasing resistance in staphylococci has created a need for alternatives to these synthetic drugs. One of the alternatives is a natural plant-based medicine for both disease prevention as well as the treatment of chronic diseases. Among such natural compounds, curcumin is one of the most studied molecules and has been an integral part of traditional medicines and Ayurveda from ancient times. It is a natural polyphenolic compound with diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancerous and antibacterial activities. In spite of its efficacy and potential, curcumin has not been approved as a therapeutic agent yet, because of its low solubility, low bioavailability, and rapid metabolism in vivo. The presence of central β-diketone moiety in curcumin is responsible for its rapid metabolism. To overcome this, in the present study, curcuminoids were designed by modifying the central β-diketone moiety of curcumin into mono carbonyl moiety and their antibacterial potency against S. aureus ATCC 29213 was determined. Further, the mode of action and hemolytic activity of the most potent curcuminoids were studied. Minimum inhibitory concentration (MIC) and in vitro killing kinetics were used to study the antibacterial activity of the designed curcuminoids. For hemolytic assay, mouse Red blood cells were incubated with curcuminoids and hemoglobin release was measured spectrophotometrically. The mode of action of curcuminoids was analysed by membrane depolarization assay using membrane potential sensitive dye 3,3’-dipropylthiacarbocyanine iodide (DiSC3(5)) through spectrofluorimetry and membrane permeabilization assay using calcein-AM through flow cytometry. Antibacterial screening of the designed library (61 curcuminoids) revealed excellent in vitro potency of six compounds against S. aureus (MIC 8 to 32 µg/ml). Moreover, these six compounds were found to be non-hemolytic up to 225 µg/ml that is much higher than their corresponding MIC values. The in vitro killing kinetics data showed five of these lead compounds to be bactericidal causing >3 log reduction in the viable cell count within 4 hrs at 5 × MIC while the sixth compound was found to be bacteriostatic. Depolarization assay revealed that all the six curcuminoids caused depolarization in their corresponding MIC range. Further, the membrane permeabilization assay showed that all the six curcuminoids caused permeabilization at 5 × MIC in 2 hrs. This membrane depolarization and permeabilization caused by curcuminoids found to be in correlation with their corresponding killing efficacy. Both these assays point out that membrane perturbations might be a primary mode of action for these curcuminoids. Overall, the present study leads us six water soluble, non-hemolytic, membrane-active curcuminoids and provided an impetus for further research on therapeutic use of these lead curcuminoids against S. aureus.
823
77114
Lower Risk of Ischemic Stroke in Hormone Therapy Users with Use of Chinese Herbal Medicine
Abstract:
Background: Little is known about the benefits and risks of use of Chinese herbal medicine (CHM) in conditions related to hormone therapy (HT) use on the risk of ischemic stroke (IS). The aim of this study is to explore the risk of IS in menopausal women treated with HT and CHM. Materials and methods: A total of 32,441 menopausal women without surgical menopause aged 40- 65 years were selected from 2003 to 2010 using the 2-million random samples of the National Health Insurance Research Database in Taiwan. According to the medication usage of HT and CHM, we divided the current and recent users into two groups: an HT use-only group (n = 4,989) and an HT/CHM group (n = 9,265). Propensity-score matching samples (4,079 pairs) were further created to deal with confounding by indication. The adjusted hazard ratios (HR) of IS during HT or CHM treatment were estimated by the robust Cox proportional hazards model. Results: The incidence rate of IS in the HT/CHM group was significantly lower than in the HT group (4.5 vs. 12.8 per 1000 person-year, p < 0.001). Multivariate analysis results indicated that additional CHM use was significant with a lower risk of IS (HR = 0.3; 95% confidence interval, 0.21-0.43). Further subgroup analyses and sensitivity analyses had similar findings. Conclusion: We found that combined use of HT and CHM was associated with a lower risk for IS than HT use only. Further study is needed to examine possible mechanism underlying this association.
822
76944
A Critical Review of the Success Model of Indian Pharmaceutical Industry
Authors:
Abstract:
The Indian Pharmaceutical Industry is ranked third largest by volume and fourteenth by value. It thus accounts for 10% of world’s production by volume and 1.5% by value according to Department of Pharmaceuticals, Government of India. The industry has shown phenomenal growth over past few years, moving from US $ 1 billion turnover in 1990 to a turnover of around US $30 billion in 2015. The Indian pharmaceutical sector is ranked seventeenth in terms of export value of active pharmaceutical ingredients and dosage forms to more than 200 countries around the globe. It has shown tremendous changes especially after Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement. Recognizing the immense potential for growth and its direct impact on Indian economy, it is important to look up the industrial policies adopted since Indian independence which turnaround the Indian pharmaceutical industry. A systematic review of changes in market structure of Indian pharmaceutical industry due to shift in policy regimes is done from 1850 to 2015 using secondary peer reviewed published research work. The aim is to understand the impact of anti-trust laws, intellectual property rights, industry competition acts and regulations are quite crucial in determining effective economic policy and have overall lasting effects on international trade and ties. The proposed paper examines the position of Indian domestic firms relative to multinational pharmaceutical firms tries to throw some light on the growth curve of Indian pharmaceutical sector.
821
76622
Management Tools for Assessment of Adverse Reactions Caused by Contrast Media at the Hospital
Abstract:
Background: Contrast media has an important role for disease diagnosis through detection of pathologies. Contrast media can, however, cause adverse reactions after administration of its agents. Although non-ionic contrast media are commonly used, the incidence of adverse events is relatively low. The most common reactions found (10.5%) were mild and manageable and/or preventable. Pharmacists can play an important role in evaluating adverse reactions, including awareness of the specific preparation and the type of adverse reaction. As most common types of adverse reactions are idiosyncratic or pseudo-allergic reactions, common standards need to be established to prevent and control adverse reactions promptly and effectively. Objective: To measure the effect of using tools for symptom evaluation in order to reduce the severity, or prevent the occurrence, of adverse reactions from contrast media. Methods: Retrospective review descriptive research with data collected on adverse reactions assessment and Naranjo’s algorithm between June 2015 and May 2016. Results: 158 patients (10.53%) had adverse reactions. Of the 1,500 participants with an adverse event evaluation, 137 (9.13%) had a mild adverse reaction, including hives, nausea, vomiting, dizziness, and headache. These types of symptoms can be treated (i.e., with antihistamines, anti-emetics) and the patient recovers completely within one day. The group with moderate adverse reactions, numbering 18 cases (1.2%), had hypertension or hypotension, and shortness of breath. Severe adverse reactions numbered 3 cases (0.2%) and included swelling of the larynx, cardiac arrest, and loss of consciousness, requiring immediate treatment. No other complications under close medical supervision were recorded (i.e., corticosteroids use, epinephrine, dopamine, atropine, or life-saving devices). Using the guideline, therapies are divided into general and specific and are performed according to the severity, risk factors and ingestion of contrast media agents. Patients who have high-risk factors were screened and treated (i.e., prophylactic premedication) for prevention of severe adverse reactions, especially those with renal failure. Thus, awareness for the need for prescreening of different risk factors is necessary for early recognition and prompt treatment. Conclusion: Studying adverse reactions can be used to develop a model for reducing the level of severity and setting a guideline for a standardized, multidisciplinary approach to adverse reactions.
820
76580
Curative Effect of Blumea lacera Leaves on Experimental Haemorrhoids in Rats
Abstract:
Hemorrhoids are one of the most common anorectal diseases around the world. Severalfactors are involved in causing hemorrhoids including irregularbowel function (constipation, diarrhea), exercise, gravity, low fiberdiet, pregnancy, obesity, high abdominal pressure, prolongedsitting, genetic factors, and aging. Pain, bleeding, itching,swelling and anal discharge are the symptoms of the disease. Due to limitedmodern pharmacotherapeutic options available for treatment, theherbal medicines remain the choice of therapy. Blumea lacera (Burm f.) DC. belonging to the Asteraceae family is a common plain land weed of Bangladesh. Traditionally it has been used for treatment of hemorrhoids.Considering the above fact, present study was aimed to validate the ethnomedicinal use of B. lacera leaves on experimental hemorrhoids in rats. The anti-hemorrhoid activity was performed by using croton oil induced rat models. The parameters studied were assessment of TNF-α and IL-6, Evans blue exudation, macroscopic severity score, recto-anal coefficient, histomorphological scores. Also, in vivo antioxidant parameters and histopathological studies were also performed. All paramaters exhibited significant anti-hemorrhoid activity. Moreover ethanolic extract of B. lacera (EBL) leaves 400mg/kg showed ameliorative effect oncroton oil induced hemorrhoids.In conclusion, EBL exhibitedbeneficial effect on croton oil- induced hemorrhoids and validates its ethnomedicinal use in treatment of piles.
819
76488
[Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors
Abstract:
Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.
818
76438
Design, Development and Characterisation of Microbeads Containing Ritinovir for Better Antiviral Therapy
Abstract:
Ritinovir, BCS class II drug, used in the treatment of HIV. The drug has shorter biological half-life of 3-5 hours and thus requires frequent dosing and ideal candidate for developing sustained release formulation. By incorporating ritinovir into a microparticulate carrier and adminstering it by oral route, it may enable the drug to present in the system for longer period of time. In the present study, an attempt has been made to formulate ritinovir loaded microbeads by ionotropic gelation method using gellan gum and chitosan. Prior to the formulation, compatibility studies using FTIR and DSC was performed to identify any possible interaction between drug and excipients. Microbeads of different ratios of drug and polymer composition were prepared and evaluated for particle size determination, drug entrapment efficiency, dynamic swelling study, in vitro dissolution study and in vivo bioavailability study. The FTIR and DSC thermogrms showed a stable character of ritinovir and polymer mixture revealed the absence of any drug polymer interactions. The crystallinity of the drug in the formulation was investigated by XRD study. The charactecteristic peaks of drug were absent in the gellan-chitsan beads indicating the probable decreased crystallinity and conversion of drug from crystalline to amorphous state in the formulation. The average particle size of microbeads was found to be in the range of 624±2.32 to 802±2.21 µm. The drug entrappment efficiency of microbeads was found to be in the range of 58±0.012 to 79.65±0.012%. The in vitro release profile of drug revealed that the best linearlity was obtained in first order plot and the mechanism of release was found to be non-fickian diffusion. The developed microbeads of ritinovir exhibited increased oral bioavailability decreased elimination rate and prolonged half-life. Therefore, the formulated microbeads of ritinovir may reduce dosing frequency, dose-related side effects and improved patient compliance in the treatment of HIV.