Next Issue
Volume 84, June
Previous Issue
Volume 84, September
Scientia Pharmaceutica is published by MDPI from Volume 84 Issue 3 (2016). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Austrian Pharmaceutical Society (Österreichische Pharmazeutische Gesellschaft, ÖPhG).

Table of Contents

Sci. Pharm., Volume 84, Issue 1 (March 2016) – 17 articles , Pages 1-230

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Order results
Result details
Select all
Export citation of selected articles as:
Open AccessArticle
Scientia Pharmaceutica, Autorenhinweise 2016
Sci. Pharm. 2016, 84(1), 219-230; https://doi.org/10.3797/scipharm.aut-16-01 - 14 Feb 2016
Viewed by 890
Abstract
Die Zeitschrift Scientia Pharmaceutica (www.scipharm.at) erscheint vierteljährlich jeweils am Quartalsende und ist ein Medium zur Publikation von Originalarbeiten, Kurzmit-teilungen und ausgewählten Übersichtsarbeiten aus allen wissenschaftlichen Disziplinen der Pharmazie und angrenzenden Gebieten sowie der pharmazeutischen Praxis.[...] Full article
Open AccessArticle
In Silico Study to Develop a Lectin-Like Protein from Mushroom Agaricus bisporus for Pharmaceutical Application
Sci. Pharm. 2016, 84(1), 203-217; https://doi.org/10.3797/scipharm.ISP.2015.11 - 14 Feb 2016
Cited by 10 | Viewed by 1535
Abstract
A lectin-like protein of unknown function designated as LSMT was recently discovered in the edible mushroom Agaricus bisporus. The protein shares high structural similarity to HA-33 from Clostridium botulinum (HA33) and Ricin-B-like lectin from the mushroom Clitocybe nebularis (CNL), which have been [...] Read more.
A lectin-like protein of unknown function designated as LSMT was recently discovered in the edible mushroom Agaricus bisporus. The protein shares high structural similarity to HA-33 from Clostridium botulinum (HA33) and Ricin-B-like lectin from the mushroom Clitocybe nebularis (CNL), which have been developed as drug carrier and anti-cancer, respectively. These homologous proteins display the ability to penetrate the intestinal epithelial cell monolayer, and are beneficial for oral administration. As the characteristics of LSMT are unknown, a structural study in silico was performed to assess its potential pharmaceutical application. The study suggested potential binding to target ligands such as HA-33 and CNL although the nature, specificity, capacity, mode, and strength may differ. Further molecular docking experiments suggest that interactions between the LSMT and tested ligands may take place. This finding indicates the possible use of the LSMT protein, initiating new research on its use for pharmaceutical purposes. Full article
Open AccessArticle
Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation
Sci. Pharm. 2016, 84(1), 191-202; https://doi.org/10.3797/scipharm.ISP.2015.10 - 14 Feb 2016
Cited by 22 | Viewed by 1182
Abstract
Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor [...] Read more.
Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacol-ogical activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. Full article
Open AccessArticle
Dissolution Profile of Mefenamic Acid Solid Dosage Forms in Two Compendial and Biorelevant (FaSSIF) Media
Sci. Pharm. 2016, 84(1), 181-190; https://doi.org/10.3797/scipharm.ISP.2015.09 - 14 Feb 2016
Cited by 6 | Viewed by 1484
Abstract
Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial [...] Read more.
Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People’s Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a ‘biorelevant’ medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator’s product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate. Full article
Open AccessArticle
Prevalence of Adverse Drug Reactions in CAD STEMI Patients Treated in the Cardiac Intensive Care Unit at the Public Hospital in Bandung, Indonesia
Sci. Pharm. 2016, 84(1), 167-179; https://doi.org/10.3797/scipharm.ISP.2015.08 - 14 Feb 2016
Viewed by 1034
Abstract
Adverse drug reactions (ADRs) are associated with morbidity, mortality, and can contribute to increased healthcare costs.This study was conducted to identify the occurence, types, and management of ADRs, as well as analyze the causal relationship, severity, and preventability of ADRs. The study was [...] Read more.
Adverse drug reactions (ADRs) are associated with morbidity, mortality, and can contribute to increased healthcare costs.This study was conducted to identify the occurence, types, and management of ADRs, as well as analyze the causal relationship, severity, and preventability of ADRs. The study was observational analysis with concurrent data collection from patients with Coronary Artery Disease-ST segment Elevation Myocardial Infarction (CAD-STEMI) treated in the Cardiac Intensive Care Unit (CICU) at a hospital in Bandung Indonesia, during the period of December 2013 to March 2014. The occurence of identified ADRs was assessed using the probability scale of Naranjo, while the severity by the scale of Hartwig and their preventability was evaluated using the scale of Schumock-Thornton. 49 ADRs were identified in 29 patients. Organ systems most affected by the ADRs were the cardiovascular and body electrolyte, each accounting for 20.41%. The hematology and gastrointestinal systems each contributed 18.37% to ADR occurrences. The causal relationship was mostly classified as “probable,” accounting for 69.39%. With regard to severity, most ADRs were classified as “moderate” at level 3, contributing to 53.06% of the occurence. In terms of preventability, most of the ADRs fell into the “non-preventable” category (79.59%). The most widely applied ADRs management was administration of an antidote or other treatments (40.82%). Further analysis revealed that the average number of drug types and duration of hospitalization significantly affected the presence of ADRs. Taken together, most patients with CAD STEMI treated in the CICU of the studied hospital experienced non-preventable ADRs and were treated with antidote or other treatments. Full article
Open AccessArticle
Cholesterol-Lowering Effect of Beta Glucan Extracted from Saccharomyces cerevisiae in Rats
Sci. Pharm. 2016, 84(1), 153-165; https://doi.org/10.3797/scipharm.ISP.2015.07 - 14 Feb 2016
Cited by 7 | Viewed by 1303
Abstract
Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan [...] Read more.
Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan is in the maintenance of yeast cell wall shape and rigidity. Studies reveal that soluble glucans can lower total cholesterol and LDL levels in patients with hypercholesterolemia. The important benefit of β-glucan is to improve the immune system and to decrease cholesterol levels in the blood. Several studies have reported the benefits of β-glucan as: antiseptic, antioxidant, anti-aging, immune system activators, protection against radiation, anti-inflammatory, anti-diabetic, anti-cholesterol etc. In this research S. cerevisiae was cultured in yeast extract–peptone–glucose (YPG) broth medium to produce beta-glucan. Cells were harvested at the stationary phase, washed, and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble β-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline–acid extraction, respectively.
Potential use of beta-glucan extract as an anticholesterol agent was tested using Sprague dawley strain rats. The experiments were divided into eight groups with four replicates: Group I (normal control), group II (fed with cholesterol without beta-glucan), group III (fed with cholesterol + atorvastatin), group IV (fed with cholesterol + β-glucan standard), group V–VIII (fed of cholesterol + β-glucan of S. cerevisiae with each dose of 10, 20, 30, and 40 mg / BW. Rats were fed with cholesterol for 14 days, except for group I. Analysis of blood was carried out to determine total cholesterol, triglycerides, and malondialdehyde. The results showed that beta-glucan crude obtained from S. cerevisiae cultures was 6.890g.L−1. Βeta-glucan extract of S. cerevisiae can reduce total cholesterol approaching normal values at doses of 10 mg of 32.79 % (blood plasma) and 33.71 % (in the liver). The extract was capable of reducing triglyceride levels in a dose of 10 mg of beta-glucan 64.43 % (blood plasma) and at a dose 30 mg of beta-glucan 19.45 % (liver). Beta-glucan treatment at a dose of 40 mg can reduce MDA levels of 45.22 % (blood plasma) and 42.64 % (liver). Full article
Open AccessArticle
Construction and Periplasmic Expression of the Anti-EGFRvIII ScFv Antibody Gene in Escherichia coli
Sci. Pharm. 2016, 84(1), 141-152; https://doi.org/10.3797/scipharm.ISP.2015.06 - 14 Feb 2016
Cited by 4 | Viewed by 1021
Abstract
In the previous study, we constructed an expression vector carrying the anti- EGFRvIII scFv antibody gene with VH-linker-VL orientation. The proteins were successfully produced in the periplasmic space of Escherichia coli. In this study, we substituted the inserted DNA [...] Read more.
In the previous study, we constructed an expression vector carrying the anti- EGFRvIII scFv antibody gene with VH-linker-VL orientation. The proteins were successfully produced in the periplasmic space of Escherichia coli. In this study, we substituted the inserted DNA with VL-linker-VH orientation of the anti- EGFRvIII scFv gene and analyzed its expression in E. coli. The DNA fragment was amplified from its cloning vector (pTz-rscFv), subsequently cloned into a previous expression vector containing the pelB signal sequence and his-tag, and then transformed into E. coli TOP10. The recombinant plasmids were characterized by restriction, PCR, and DNA sequencing analyses. The new anti-EGFRvIII scFv antibody proteins have been successfully expressed in the periplasmic compartment of E. coli Nico21(DE3) using 0.1 mM final concentration of IPTG induction. Total proteins, soluble periplasmic and cytoplasmic proteins, solubilized inclusion bodies, and extracellular proteins were analyzed by SDS-PAGE and Western Blot analyses. The results showed that soluble scFv proteins were found in all fractions except from the cytoplasmic space. Full article
Open AccessArticle
In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion
Sci. Pharm. 2016, 84(1), 131-140; https://doi.org/10.3797/scipharm.ISP.2015.05 - 14 Feb 2016
Cited by 12 | Viewed by 1538
Abstract
Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated [...] Read more.
Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hyper-cholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self-nanoemulsifying carrier, it slightly increased the inhibitory effect on ACE. In contrast, the effect of curcumin in reducing cholesterol based on the HMGR assay was more pronounced. Curcumin encapsulated in a nanoemulsion showed significant cholesterol-lowering activity compared to a standard drug, pravastatin. Therefore, we conclude that curcumin does not show ACE inhibitory effects, but has potential use as an alternative therapeutic compound to treat hyperlipidaemia. Curcumin encapsulated in a nanoemulsion increased not only the HMGR inhibition, but also ACE inhibition of curcumin. These effects are suggested to be the result of improved solubility in the nanoemulsion system. Full article
Open AccessArticle
Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better
Sci. Pharm. 2016, 84(1), 113-130; https://doi.org/10.3797/scipharm.ISP.2015.04 - 14 Feb 2016
Viewed by 835
Abstract
Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. [...] Read more.
Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhIFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT1, and DNA expression of caspase 3. Full article
Open AccessArticle
Detection of HER2 Gene Polymorphism in Breast Cancer: PCR Optimization Study
Sci. Pharm. 2016, 84(1), 103-111; https://doi.org/10.3797/scipharm.ISP.2015.03 - 14 Feb 2016
Cited by 4 | Viewed by 936 | Correction
Abstract
Cancers are the most deadly diseases in the world and their incidences continue to increase over time. Particularly, breast cancer in females places 1st rank among other types of cancers in term of cancer cases (23%) and death incidence (14%). Recent findings [...] Read more.
Cancers are the most deadly diseases in the world and their incidences continue to increase over time. Particularly, breast cancer in females places 1st rank among other types of cancers in term of cancer cases (23%) and death incidence (14%). Recent findings support the correlation between Ile655Val SNP in the HER2 gene with breast cancer risk. Moreover, the Ile655Val HER2 gene polymorphism could be a predictive factor in a neoadjuvant therapy setting. Precise detection of the Ile655Val HER2 gene SNP in early breast cancer patients will be beneficial in designing the most suitable treatment and in increasing the efficacy of anticancer drugs. Here we develop a rapid and inexpensive method for Ile655Val SNP detection in the HER2 gene based on allele-specific PCR technology. Two forward primers and one common reverse primer were designed to anneal specifically either on the HER2 gene fragment containing the GG genotype or to the HER2 gene fragment containing the AA genotype where one of these primers had been added with poly-GC at 5’ upstream. Moreover, to increase discrimination level, mismatch bases at the SNP site and the 3rd base of each forward primers from 3’end were added. To test the performance of the designed primers in discriminating a polymorphism and its annealing temperature, breast cancer specimen-derived genomic DNA (with GG genotype) and pGEM_HER2/AA (with AA genotype) were used as templates in the PCR reaction. The optimal annealing temperature for SNP detection was at 51.5°C as showed by the appearance of a 150 base pair (bp) band as AA genotype (pGEM_HER2/AA template), 116bp band as GG genotype (genomic DNA template), and both types of bands as AG genotype (mix of pGEM_HER2/AA and genomic DNA template). Allelic types of breast cancer patients were also determined using this optimized method compared to sanger sequencing. The 100% accordance was shown for all types of genotypes in both methods. The allele-specific PCR in this study may have application in determining polymorphisms of the breast cancers-originated Ile655Val HER2 gene. Full article
Open AccessArticle
Plasmid Copy Number Determination by Quantitative Polymerase Chain Reaction
Sci. Pharm. 2016, 84(1), 89-101; https://doi.org/10.3797/scipharm.ISP.2015.02 - 14 Feb 2016
Cited by 8 | Viewed by 1058
Abstract
Recombinant therapeutic proteins are biopharmaceutical products that develop rapidly for years. Recombinant protein production in certain hosts requires vector expression harboring the gene encoding the corresponding protein. Escherichia coli is the prokaryote organism mostly used in recombinant protein production, commonly using a plasmid [...] Read more.
Recombinant therapeutic proteins are biopharmaceutical products that develop rapidly for years. Recombinant protein production in certain hosts requires vector expression harboring the gene encoding the corresponding protein. Escherichia coli is the prokaryote organism mostly used in recombinant protein production, commonly using a plasmid as the expression vector. Recombinant protein production is affected by plasmid copy number harboring the encoded gene, hence the determination of plasmid copy number also plays an important role in establishing a recombinant protein production system. On the industrial scale, a low copy number of plasmids are more suitable due to their better stability. In the previous study we constructed pCAD, a plasmid derived from the low copy number pBR322 plasmid. This study was aimed to confirm pCAD’s copy number by quantitative polymerase chain reaction (qPCR). Plasmid copy number was determined by comparing the quantification signal from the plasmid to those from the chromosome. Copy number was then calculated by using a known copy number plasmid as a standard. Two pairs of primers, called tdk and ori, were designed for targeting a single gene tdk in the chromosome and a conserved domain in the plasmid’s ori, respectively. Primer quality was analyzed in silico using PrimerSelect DNASTAR and PraTo software prior to in vitro evaluation on primer specificity and efficiency as well as optimization of qPCR conditions. Plasmid copy number determination was conducted on E. coli lysates harboring each plasmid, with the number of cells ranging from 102–105 cells/μL. Cells were lysed by incubation at 95ºC for 10 minutes, followed by immediate freezing at −4°C. pBR322 plasmid with the copy number of ~19 copies/cell was used as the standard, while pJExpress414-sod plasmid possessing the high copy number pUC ori was also determined to test the method being used. In silico analysis based on primer-primer and primer-template interactions showed that both primer pairs were acceptable and were predicted to have good performance. Those predictions were in agreement with the in vitro test that gave a single band in the PCR product’s electropherogram and a single peak in DNA amplicon’s melting curve with a Tm value of 79.01 ± 0.11°C for the tdk primer and 81.53 ± 0.29°C for the ori primer. The efficiency of each primer was 1.95 and 1.97, respectively. The calculation result of pCAD’s copy number was 13.1 ± 0.3 copies/cell, showing that pCAD’s low copy number has been determined and confirmed. Meanwhile, it was 576.3 ± 91.9 copies/cell for pJExpress414-sod, in accordance with the hypothesis that pUC ori regulates the high copy number plasmid. In conclusion, the designed primers and qPCR conditions used in this study can be used to determine plasmid copy number for plasmids with pBR322 and pUC ori. The method should be tested further on plasmids harboring other type of ori. Full article
Open AccessArticle
Study of HMG-CoA Reductase Inhibition Activity of the Hydrolyzed Product of Snakehead Fish (Channa striata) Skin Collagen with 50 kDa Collagenase from Bacillus licheniformis F11.4
Sci. Pharm. 2016, 84(1), 81-88; https://doi.org/10.3797/scipharm.ISP.2015.01 - 14 Feb 2016
Cited by 3 | Viewed by 923
Abstract
Bioactive peptides produced from enzymatic hydrolysis fibrous protein have been proven to have several biological activities. Previous study showed that the hydrolysis product of snakehead fish skin collagen with 26 kDa collagenase from Bacillus licheniformis F11.4 showed HMG-CoA (HMGR) inhibition activity. The aim [...] Read more.
Bioactive peptides produced from enzymatic hydrolysis fibrous protein have been proven to have several biological activities. Previous study showed that the hydrolysis product of snakehead fish skin collagen with 26 kDa collagenase from Bacillus licheniformis F11.4 showed HMG-CoA (HMGR) inhibition activity. The aim of this research was to determine the ability of the hydrolysis product produced from snakehead fish skin collagen hydrolysed by 50 kDa collagenase from B. licheniformis F11.4 in inhibiting HMGR activity. Snakehead fish skin collagen was extracted using an acid method and collagenase was produced from B. licheniformis F11.4 using half-strength Luria Bertani (LB) medium containing 5% collagen. Crude collagenase was concentrated and fractionated using the DEAE Sephadex A-25 column eluted with increasing gradient concentrations of NaCl. Collagen, collagenase, and fractions were analyzed using SDS-PAGE and collagenolytic activity was analyzed by the zymography method. Collagenase with 50 kDa molecular weight presented in fraction one was used to hydrolyze the collagen. The reaction was done in 18 hours at 50°C. The hydrolysis product using 3.51 μg collagen and 9 ng collagenase showed 25.8% inhibition activity against pravastatin. This work shows for the first time that the hydrolysis product of snakehead fish skin collagen and 50 kDa collagenase from B. licheniformis F11.4 has potential as an anticholesterol agent. Full article
Open AccessArticle
Evaluation and Comparison of the In Vitro Cytotoxic Activity of Withania somnifera Methanolic and Ethanolic Extracts against MDA-MB-231 and Vero Cell Lines
Sci. Pharm. 2016, 84(1), 41-59; https://doi.org/10.3797/scipharm.1507-13 - 26 Sep 2015
Cited by 14 | Viewed by 1172
Abstract
Withania somnifera Dunal (WS), commonly known as Ashwagandha in India, belongs to the family Solanaceae. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. In the current study, the in vitro cytotoxic activity of methanolic, ethanolic, and aqueous extracts [...] Read more.
Withania somnifera Dunal (WS), commonly known as Ashwagandha in India, belongs to the family Solanaceae. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. In the current study, the in vitro cytotoxic activity of methanolic, ethanolic, and aqueous extracts of WS stems was evaluated using cytometry and the MTT assay against the MDA-MB-231 human breast cancer cell line. Methanolic and ethanolic extracts of WS showed potent anticancer activity on the MDA-MB-231 human breast cancer cell line, whereas the aqueous extract did not exhibit any significant activity at 100 μg/ml. The percentage viability of the cell lines was determined by using the Trypan blue dye exclusion method. Cell viability was reduced to 21% and 0% at 50 and 100 μg/ml of the methanolic extract, respectively, as compared to 19% and 0% at 50 and 100 μg/ml for the ethanolic extract and 37% at 100 μg/ml in sterile Milli-Q water after 48 hours of treatment. Methanolic and ethanolic extracts of WS were shown to possess IC50 values of 30 and 37 μg/ml, respectively, by the MTT assay and cytometer-based analysis, with the methanolic extract being more active than the other two. On the other hand, methanolic and ethanolic extracts of WS did not exhibit any significant in vitro activity against the normal epithelial cell line Vero at 50 μg/ml. HPLC was carried out for the analysis of its phytochemical profile and demonstrated the presence of the active component Withaferin A in both extracts. The methanolic and ethanolic extracts of Withania should be studied further for the isolation and characterization of the active components to lead optimization studies. Full article
Open AccessArticle
Criteria for Drug Pricing: Preliminary Experiences with Modeling the Price-Volume Relationship
Sci. Pharm. 2016, 84(1), 73-79; https://doi.org/10.3797/scipharm.1506-03 - 27 Aug 2015
Cited by 4 | Viewed by 830
Abstract
In managing drug prices at the national level, price-volume agreements are a tool aimed at ensuring sustainability in cases where the drug price is high and the population is large. These agreements in fact determine a progressive price reduction as more and more [...] Read more.
In managing drug prices at the national level, price-volume agreements are a tool aimed at ensuring sustainability in cases where the drug price is high and the population is large. These agreements in fact determine a progressive price reduction as more and more patients are treated. Price decays in this context generally have a purely empirical nature, but a theoretical basis would be needed.
The present paper describes a simple model that manages price-volume agreements. Two real examples (ranibizumab for macular degeneration and sofosbuvir for hepatitis C) are analysed in detail. The objective of our analysis was to identify some objective criteria to rationally guide these agreements and to convert these criteria into explicit quantitative rules. Full article
Open AccessArticle
Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives
Sci. Pharm. 2016, 84(1), 1-18; https://doi.org/10.3797/scipharm.1507-02 - 18 Aug 2015
Cited by 2 | Viewed by 907
Abstract
The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a–i) and sulfoxide (5a–h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a–i) and sulfoxide [...] Read more.
The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a–i) and sulfoxide (5a–h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a–i) and sulfoxide (5a–h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides. Full article
Open AccessArticle
Hyaluronan–Itaconic Acid–Glutaraldehyde Films for Biomedical Applications: Preliminary Studies
Sci. Pharm. 2016, 84(1), 61-72; https://doi.org/10.3797/scipharm.1504-17 - 29 Jul 2015
Cited by 4 | Viewed by 852
Abstract
New hyaluronic acid–itaconic acid films were synthesized as potential materials with biomedical applications. In this work, we explored the homogeneous cross-linking reactions of hyaluronic acid using glutaraldehyde in the presence of itaconic acid and triacetin as plasticizers.
Biomechanical properties were assessed in terms [...] Read more.
New hyaluronic acid–itaconic acid films were synthesized as potential materials with biomedical applications. In this work, we explored the homogeneous cross-linking reactions of hyaluronic acid using glutaraldehyde in the presence of itaconic acid and triacetin as plasticizers.
Biomechanical properties were assessed in terms of stability by measuring swelling in aqueous environments, investigating wettability using contact angle tests, and evaluating bioadhesive performance. The ductility of the materials was evaluated through stress-strain measurements and the morphology was explored by scanning electron microscopy.
The results show that the incorporation of itaconic acid improved most of the desirable properties, increasing adhesiveness and reducing wettability and swelling. The use of triacetin enhanced the strength, bioadhesiveness, and ductility of the material. Full article
Open AccessArticle
Novel, Precise, Accurate Ion-Pairing Method to Determine the Related Substances of the Fondaparinux Sodium Drug Substance: Low-Molecular-Weight Heparin
Sci. Pharm. 2016, 84(1), 19-40; https://doi.org/10.3797/scipharm.1505-20 - 22 Jul 2015
Cited by 1 | Viewed by 987
Abstract
Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and [...] Read more.
Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and validated by a novel ion-pair HPLC method. The separation of the drug and its degradation products was achieved with the polymer-based PLRPs column (250 mm × 4.6 mm; 5 μm) in gradient elution mode. The mixture of 100 mM n-hexylamine and 100 mM acetic acid in water was used as buffer solution. Mobile phase A and mobile phase B were prepared by mixing the buffer and acetonitrile in the ratio of 90:10 (v/v) and 20:80 (v/v), respectively. Mobile phases were delivered in isocratic mode (2% B for 0–5 min) followed by gradient mode (2–85% B in 5–60 min). An Evaporative Light Scattering Detector (ELSD) was connected to the LC system to detect the responses of chromatographic separation. Further, the drug was subjected to stress studies for acidic, basic, oxidative, photolytic, and thermal degradations as per ICH guidelines and the drug was found to be labile in acid, base hydrolysis, and oxidation, while stable in neutral, thermal, and photolytic degradation conditions. The method provided linear responses over the concentration range of the LOQ to 0.30% for each impurity with respect to the analyte concentration of 12.5 mg/mL, and regression analysis showed a correlation coefficient value (r2) of more than 0.99 for all the impurities. The LOD and LOQ were found to be 1.4 μg/mL and 4.1 μg/mL, respectively, for fondaparinux. The developed ion-pair method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness Full article
Previous Issue
Next Issue
Back to TopTop