cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.7974173.v1
title: Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: A systematic review of case reports

description: The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.
DOI: 10.6084/m9.figshare.7974185
title: Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity

description: All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.
DOI: 10.6084/m9.figshare.7974185.v1
title: Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity

description: All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.
DOI: 10.6084/m9.figshare.7974122
title: Developed and validated stability indicating HPLC method for the determination of epirubicin in bulk drug, marketed injection and polymeric nanoparticles

description: Present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for routine quality control of epirubicin (EPI) in bulk drug, marketed injections and polymeric nanoparticles. Separation was carried out by C18 column. Isocratic elution was carried out using mobile phase A: 0.16% o-phosphoric acid solution, B: acetonitrile and methanol mixture (80:20, v/v) in the ratio of 60:40 (A: B) while the flow rate was maintained at 1mL/min. Analyses were performed at 233.5 nm using PDA detector. Excellent linear relationship was observed between peak-area versus drug concentration in the range of 1.0-100.0 μg/mL (r2, 0.999). Developed method was found to be sensitive (Limits of detection and quantification were found to be ~8 ng/mL and ~25 ng/mL, respectively), precise (RSD &lt;1.0%, for repeatability and &lt;2.0% for intermediate precision, within acceptable ranges of precision), accurate (recovery in different dosage form, 94.65 -100.26%, within acceptable range, 80-120%), specific and robust (% RSD &lt;2, for system suitability parameters). Stress-induced degradation studies demonstrated that method can suitability be applied in the presence of degradants. Developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro release profile, in vitro permeation studies as well as stability assessment of polymeric nanoparticles.
DOI: 10.6084/m9.figshare.7974122.v1
title: Developed and validated stability indicating HPLC method for the determination of epirubicin in bulk drug, marketed injection and polymeric nanoparticles

description: Present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for routine quality control of epirubicin (EPI) in bulk drug, marketed injections and polymeric nanoparticles. Separation was carried out by C18 column. Isocratic elution was carried out using mobile phase A: 0.16% o-phosphoric acid solution, B: acetonitrile and methanol mixture (80:20, v/v) in the ratio of 60:40 (A: B) while the flow rate was maintained at 1mL/min. Analyses were performed at 233.5 nm using PDA detector. Excellent linear relationship was observed between peak-area versus drug concentration in the range of 1.0-100.0 μg/mL (r2, 0.999). Developed method was found to be sensitive (Limits of detection and quantification were found to be ~8 ng/mL and ~25 ng/mL, respectively), precise (RSD &lt;1.0%, for repeatability and &lt;2.0% for intermediate precision, within acceptable ranges of precision), accurate (recovery in different dosage form, 94.65 -100.26%, within acceptable range, 80-120%), specific and robust (% RSD &lt;2, for system suitability parameters). Stress-induced degradation studies demonstrated that method can suitability be applied in the presence of degradants. Developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro release profile, in vitro permeation studies as well as stability assessment of polymeric nanoparticles.
DOI: 10.6084/m9.figshare.7974470
title: Antibacterial, anti fungal and E. coli DNA cleavage of Euphorbia prostrata and Pelargonium graveolens extract and their combination with novel nanoparticles

description: As there are a lot of antibacterial and anti-fungal resistant pathogens, researchers attempt to substitute antimicrobial drugs with various medical plants and novel nanoparticles. The present study was conducted to characterize antimicrobial activities of Euphorbia prostrata and Pelargonium graveolens extract alone and in combination with Mn-Ni@Fe3O4-NPs & Mn: Fe (OH)3-NPs on the DNA cleavage of E. coli and also Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Candida albicans. The effects of antimicrobial activities on above scenarios were evaluated using disc diffusion, MIC, MBC, and E. coli DNA electrophoresis methods. The results showed that the effects of antibacterial assay values of Euphorbia prostrata & Mn: Fe(OH)3 was 21.00 mm for E. coli and while it was 19.5 mm for Euphorbia prostrata & Mn-Ni@Fe3O4 against Pseudomonas aeruginosa at a concentration of 100mg/mL. The highest level of DNA cleavage was seen in mixed of Euphorbia prostrata & Mn: Fe(OH)3 nanoparticles. In conclusion, the combination of Euphorbia prostrata and Pelargonium graveolens extracts with nanostructures showed synergic effects on eliminating the bacteria via DNA destruction and others mechanisms. Moreover, the synergistic effect of nanoparticles with plant extracts seems to bring about new choices for the treatment of infectious diseases.
DOI: 10.6084/m9.figshare.7974470.v1
title: Antibacterial, anti fungal and E. coli DNA cleavage of Euphorbia prostrata and Pelargonium graveolens extract and their combination with novel nanoparticles

description: As there are a lot of antibacterial and anti-fungal resistant pathogens, researchers attempt to substitute antimicrobial drugs with various medical plants and novel nanoparticles. The present study was conducted to characterize antimicrobial activities of Euphorbia prostrata and Pelargonium graveolens extract alone and in combination with Mn-Ni@Fe3O4-NPs & Mn: Fe (OH)3-NPs on the DNA cleavage of E. coli and also Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Candida albicans. The effects of antimicrobial activities on above scenarios were evaluated using disc diffusion, MIC, MBC, and E. coli DNA electrophoresis methods. The results showed that the effects of antibacterial assay values of Euphorbia prostrata & Mn: Fe(OH)3 was 21.00 mm for E. coli and while it was 19.5 mm for Euphorbia prostrata & Mn-Ni@Fe3O4 against Pseudomonas aeruginosa at a concentration of 100mg/mL. The highest level of DNA cleavage was seen in mixed of Euphorbia prostrata & Mn: Fe(OH)3 nanoparticles. In conclusion, the combination of Euphorbia prostrata and Pelargonium graveolens extracts with nanostructures showed synergic effects on eliminating the bacteria via DNA destruction and others mechanisms. Moreover, the synergistic effect of nanoparticles with plant extracts seems to bring about new choices for the treatment of infectious diseases.
DOI: 10.6084/m9.figshare.7974821
title: Anti-Sporothrix brasiliensis activity of different pyrazinoic acid prodrugs: a repurposing evaluation

description: From drug repurposing studies, this work aimed to evaluate the activity of different pyrazinoic acid (POA) derivatives against Sporothrix brasiliensis. The POA esters were prepared and characterized as previously reported by classical esterification reactions, with good to excellent yields. Sporothrix brasiliensis isolates from cats (n=6) and standard strains of S. brasiliensis and S. schenckii were used to assess the antifungal activity of the POA derivatives through broth microdilution assay (CLSI M38-A2). Among the tested compounds, molecules 3 and 4 showed fungistatic and fungicidal activities against all Sporothrix spp. strains, and the obtained MIC and MFC values ranged from 2.12 to 4.24 mg/mL and from 1.29 to 5.15 mg/mL, respectively. Compound 2 and 5 were active as in vitro inhibitors of fungal growth, but showed weak fungicidal activity, while molecules 1 and POA itself were inactive. The results suggest the activity of POA derivatives against Sporothrix spp. may be dependent on the lipophilicity. In addition, the antifungal susceptibility of the isolates to itraconazole was performed, showing that two Sporothrix isolates from cats were itraconazole-resistant. Compounds 3 and 4 were also active against these itraconazole-resistant isolates, indicating a possible alternative route to the standard mode of action of itraconazole.
DOI: 10.6084/m9.figshare.7974821.v1
title: Anti-Sporothrix brasiliensis activity of different pyrazinoic acid prodrugs: a repurposing evaluation

description: From drug repurposing studies, this work aimed to evaluate the activity of different pyrazinoic acid (POA) derivatives against Sporothrix brasiliensis. The POA esters were prepared and characterized as previously reported by classical esterification reactions, with good to excellent yields. Sporothrix brasiliensis isolates from cats (n=6) and standard strains of S. brasiliensis and S. schenckii were used to assess the antifungal activity of the POA derivatives through broth microdilution assay (CLSI M38-A2). Among the tested compounds, molecules 3 and 4 showed fungistatic and fungicidal activities against all Sporothrix spp. strains, and the obtained MIC and MFC values ranged from 2.12 to 4.24 mg/mL and from 1.29 to 5.15 mg/mL, respectively. Compound 2 and 5 were active as in vitro inhibitors of fungal growth, but showed weak fungicidal activity, while molecules 1 and POA itself were inactive. The results suggest the activity of POA derivatives against Sporothrix spp. may be dependent on the lipophilicity. In addition, the antifungal susceptibility of the isolates to itraconazole was performed, showing that two Sporothrix isolates from cats were itraconazole-resistant. Compounds 3 and 4 were also active against these itraconazole-resistant isolates, indicating a possible alternative route to the standard mode of action of itraconazole.
DOI: 10.6084/m9.figshare.7974740
title: The appropriate use of human albumin in a Brazilian University Hospital: therapeutic indication and dosage regimen

description: The objective of the study was to evaluate the use of human albumin in a Brazilian university hospital, in compliance with the institutional protocol and other clinical guidelines, taking into account the therapeutic indications and the dosage regimens. Data was obtained from the pharmacy dispensing records of human albumin, the requests for use it and, when available, the patient’s records between January and October 2017. After evaluation the therapeutic indications and the dosage regimens were classified as “appropriate” and “inappropriate”. The analysis of 98 requests showed that, when compared to the institutional protocol, 54 (55.1%) requests had an inappropriate therapeutic indication. However, when a comparison was made between 25 medical records (54 requests) and other clinical guidelines, it was observed that the therapeutic indication had none classified as inappropriate. In addition, 16 (29.7%) requests were considered inappropriate in relation to dosage regimens. From these results, it was possible to conclude that although the use of human albumin in the hospital was associated to a clinical protocol, it was outdated. Thus, it is possible to affirm that not only the adoption of a clinical protocol, but its periodical updating is an important strategy to promote the rational use of drugs.
DOI: 10.6084/m9.figshare.7974740.v1
title: The appropriate use of human albumin in a Brazilian University Hospital: therapeutic indication and dosage regimen

description: The objective of the study was to evaluate the use of human albumin in a Brazilian university hospital, in compliance with the institutional protocol and other clinical guidelines, taking into account the therapeutic indications and the dosage regimens. Data was obtained from the pharmacy dispensing records of human albumin, the requests for use it and, when available, the patient’s records between January and October 2017. After evaluation the therapeutic indications and the dosage regimens were classified as “appropriate” and “inappropriate”. The analysis of 98 requests showed that, when compared to the institutional protocol, 54 (55.1%) requests had an inappropriate therapeutic indication. However, when a comparison was made between 25 medical records (54 requests) and other clinical guidelines, it was observed that the therapeutic indication had none classified as inappropriate. In addition, 16 (29.7%) requests were considered inappropriate in relation to dosage regimens. From these results, it was possible to conclude that although the use of human albumin in the hospital was associated to a clinical protocol, it was outdated. Thus, it is possible to affirm that not only the adoption of a clinical protocol, but its periodical updating is an important strategy to promote the rational use of drugs.
DOI: 10.6084/m9.figshare.7336637
title: Active ingredients, mechanisms of action and efficacy tests of antipollution cosmetic and personal care products

description: Urban population around the globe is direct exposed to the pollution caused by several sources (vehicles, industries, smokes etc.) and primary pollutants are divided in particulate matter and toxic gases. Current researches in populous countries indicated that exposure to pollution could affect sebum composition, stratum corneum quality and signs of skin aging. Hair and scalp are also affected by the excessive exposure to pollutants, resulting in a dull, dry and lifeless appearance. Cosmetics have been evolved conceptual and scientifically to achieve substantial effectiveness against pollution damaging on the cutaneous tissue, involving the development of innovative multipurpose active ingredients and efficacy tests, skilled to prove the protection and benefits of such personal care products. In this review, we highlighted the skin and hair/scalp damages provoked by the main environmental pollutants and the active substances used in antipollution cosmetics/personal care products with the respective mechanisms of action. Likewise, in vitro and in vivo efficacy tests were discussed concerning the antipollution claim substantiating.
DOI: 10.6084/m9.figshare.7336637.v1
title: Active ingredients, mechanisms of action and efficacy tests of antipollution cosmetic and personal care products

description: Urban population around the globe is direct exposed to the pollution caused by several sources (vehicles, industries, smokes etc.) and primary pollutants are divided in particulate matter and toxic gases. Current researches in populous countries indicated that exposure to pollution could affect sebum composition, stratum corneum quality and signs of skin aging. Hair and scalp are also affected by the excessive exposure to pollutants, resulting in a dull, dry and lifeless appearance. Cosmetics have been evolved conceptual and scientifically to achieve substantial effectiveness against pollution damaging on the cutaneous tissue, involving the development of innovative multipurpose active ingredients and efficacy tests, skilled to prove the protection and benefits of such personal care products. In this review, we highlighted the skin and hair/scalp damages provoked by the main environmental pollutants and the active substances used in antipollution cosmetics/personal care products with the respective mechanisms of action. Likewise, in vitro and in vivo efficacy tests were discussed concerning the antipollution claim substantiating.
DOI: 10.6084/m9.figshare.7336697
title: Computational drug discovery for the Zika virus

description: Few Zika virus (ZIKV) outbreaks had been reported since its first detection in 1947, until the recent epidemics occurred in South America (2014/2015) and expeditiously became a global public health emergency. This arbovirus reached 0.5-1.3 million cases of ZIKV infection in Brazil in 2015 and rapidly spread in new geographic areas such as the Americas. Despite the mild symptoms of the Zika fever, the major concern is related to the related severe neurological disorders, especially microcephaly in newborns. Advances in ZIKV drug discovery have been made recently and constitute promising approaches to ZIKV treatment. In this review, we summarize current computational drug discovery efforts and their applicability to discovery of anti-ZIKV drugs. Lastly, we present successful examples of the use of computational approaches to ZIKV drug discovery.
DOI: 10.6084/m9.figshare.7336697.v1
title: Computational drug discovery for the Zika virus

description: Few Zika virus (ZIKV) outbreaks had been reported since its first detection in 1947, until the recent epidemics occurred in South America (2014/2015) and expeditiously became a global public health emergency. This arbovirus reached 0.5-1.3 million cases of ZIKV infection in Brazil in 2015 and rapidly spread in new geographic areas such as the Americas. Despite the mild symptoms of the Zika fever, the major concern is related to the related severe neurological disorders, especially microcephaly in newborns. Advances in ZIKV drug discovery have been made recently and constitute promising approaches to ZIKV treatment. In this review, we summarize current computational drug discovery efforts and their applicability to discovery of anti-ZIKV drugs. Lastly, we present successful examples of the use of computational approaches to ZIKV drug discovery.
DOI: 10.6084/m9.figshare.7336709
title: Design of Experiments (DoE) applied to Pharmaceutical and Analytical Quality by Design (QbD)

description: According to Quality by Design (QbD) concept, quality should be built into product/method during pharmaceutical/analytical development. Usually, there are many input factors that may affect quality of product and methods. Recently, Design of Experiments (DoE) have been widely used to understand the effects of multidimensional and interactions of input factors on the output responses of pharmaceutical products and analytical methods. This paper provides theoretical and practical considerations for implementation of Design of Experiments (DoE) in pharmaceutical and/or analytical Quality by Design (QbD). This review illustrates the principles and applications of the most common screening designs, such as two-level full factorial, fractionate factorial, and Plackett-Burman designs; and optimization designs, such as three-level full factorial, central composite designs (CCD), and Box-Behnken designs. In addition, the main aspects related to multiple regression model adjustment were discussed, including the analysis of variance (ANOVA), regression significance, residuals analysis, determination coefficients (R2, R2-adj, and R2-pred), and lack-of-fit of regression model. Therefore, DoE was presented in detail since it is the main component of pharmaceutical and analytical QbD.