scholarly journals New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mariana P. Miranda-Hernández ◽  
Carlos A. López-Morales ◽  
Francisco C. Perdomo-Abúndez ◽  
Rodolfo D. Salazar-Flores ◽  
Nancy D. Ramírez-Ibanez ◽  
...  
Keyword(s):  
Reference Product ◽  
Biological Properties ◽  
Convincing Evidence ◽  
Order Structure ◽  
Immunomodulatory Activity ◽  
Comparability Exercise ◽  
Glycan Heterogeneity ◽  
Clinical Comparability ◽  
High Degree

Etanercept is a recombinant fusion protein approved for the treatment of TNF-αmediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in theirin vitroactivity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA.

scholarly journals Physicochemical and Biological Characterization of a Biosimilar Trastuzumab

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Carlos A. López-Morales ◽  
Mariana P. Miranda-Hernández ◽  
L. Carmina Juárez-Bayardo ◽  
Nancy D. Ramírez-Ibáñez ◽  
Alexis J. Romero-Díaz ◽  
...  
Keyword(s):  
Reference Product ◽  
World Health ◽  
Malignant Neoplasms ◽  
Pharmacological Studies ◽  
Comparability Exercise ◽  
Potential Impact ◽  
Health Organization ◽  
High Degree ◽  
Degree Of Similarity

According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.

scholarly journals The in vitro Immunomodulatory Activity of Oleuropein, a Secoiridoid Glycoside from Olea europaea L

2007 ◽  
Vol 2 (5) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Andrew Mangion Randon ◽  
Everaldo Attard
Keyword(s):  
Olea Europaea ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Dose Dependence ◽  
Immunomodulatory Activity ◽  
In Vitro Effects ◽  
High Degree ◽  
Secoiridoid Glycoside ◽  
Olea Europaéa

Oleuropein, a secoiridoid glycoside, is a potential antioxidant and antimicrobial agent. The aim of the present study was to investigate the in vitro effects of oleuropein and Olea europaea extracts on unstimulated lymphocytes. Oleuropein did not produce any significant cytotoxic effects on lymphocytes. On the contrary, it had a stimulatory effect, and was capable of inducing and maintaining high proliferation rates in lymphocytes. The stimulatory effects of oleuropein and extracts were concentration-dependent with a range of median stimulatory concentration 1 mM at 48 h. The cytotoxicity effect of oleuropein and extracts increased with time resulting in a greater cytotoxic effect on already-stimulated lymphocytes at 96 h even though dose dependence was not demonstrated. Morphological observations showed that oleuropein and extracts induced blastogenesis similar to that of phytohaemagglutinin (PHA). In fact, from lymphocyte activation studies, oleuropein exhibited a high degree of lymphocyte aggregation, which is an indicator of cell activation and proliferation.

In vitro Behaviour of Alumina-Hydroxiapatite Composites Coatings

2018 ◽  
Vol 69 (6) ◽  
pp. 1416-1418
Author(s):  
Alexandru Szabo ◽  
Ilare Bordeasu ◽  
Ion Dragos Utu ◽  
Ion Mitelea
Keyword(s):  
Pure Titanium ◽  
Titanium Substrate ◽  
High Strength ◽  
Biological Properties ◽  
Commercially Pure Titanium ◽  
Hvof Spraying ◽  
Before And After ◽  
Sbf Solution ◽  
Oxygen Fuel

Hydroxyapatite (HA) is a very common material used for biomedical applications. Usually, in order to improve its poor mechanical properties is combined or coated with other high-strength materials.The present paper reports the manufacturing and the biocompatibility behaviour of two different biocomposite coatings consisting of alumina (Al2O3) and hydroxyapatite (HA) using the high velocity oxygen fuel (HVOF) spraying method which were deposited onto the surface of a commercially pure titanium substrate. The biological properties of the Al2O3-HA materials were evaluated by in vitro studies. The morphology of the coatings before and after their immersing in the simulated body fluid (SBF) solution was characterized by scanning electron microscopy (SEM). The results showed an important germination of the biologic hydroxyapatite crystallite on the surface of both coatings.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

PDO Rotonda’s Red Eggplant Extract: In vitro Determination of Biological Properties and Minerals Bioaccessibility

2020 ◽  
Vol 16 (1) ◽  
pp. 65-74
Author(s):  
Ortensia Ilaria Parisi ◽  
Mariarosa Ruffo ◽  
Fabio Amone ◽  
Rocco Malivindi ◽  
Domenico Gorgoglione ◽  
...  
Keyword(s):  
Control Sample ◽  
Specific Area ◽  
Biological Properties ◽  
Ammonium Molybdate ◽  
Antihypertensive Activity ◽  
Protected Designation Of Origin ◽  
The Family ◽  
Oil Red O Staining

Background: The Rotonda’s Red Eggplant belongs to the family of Solanum aethiopicum and it is cultivated in a specific area of Potenza (Basilicata, South of Italy) including villages of Rotonda, Viggianello, Castelluccio Superiore and Castelluccio Inferiore. The Red Eggplant cultivated in this area has gained the PDO, “Protected Designation of Origin”. Objective: The aim of this research was to evaluate the use of PDO Rotonda’s Red Eggplant extract as a possible nutraceutical supplement. The antioxidant, antihypertensive, hypoglycemic, and hypolipidemic properties were in vitro evaluated. Methods: The antioxidant activity was investigated by evaluating the scavenging properties against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and by performing the Ammonium Molybdate and Folin-Ciocalteu assay. The hypoglycemic and antihypertensive activity was studied by evaluating the α-Amylase, α-Glucosidase and Angiotensin Converting Enzyme, respectively, inhibiting activity. In order to evaluate the hypolipidemic activity, the pancreatic lipase inhibiting property was determined and Oil Red O staining assay was performed. Finally, to evaluate the possible use of this extract as a minerals supplement, Selenium, Potassium and Chrome bioaccessibility was studied. Results: The obtained results underline the good antioxidant, hypoglycemic, antihypertensive and hypolipidemic in vitro properties of the PDO Rotonda’s Red Eggplant extract. Moreover, the obtained data show a higher minerals bioaccessibility and this higher value could be ascribable to the natural phytocomplex of PDO Rotonda’s Red Eggplant, which increases the minerals bioaccessibility if compare it with a control sample. Conclusion: The obtained results show that PDO Rotonda’s Red Eggplant extract, might be used as a possible nutraceutical supplement, along with traditional therapies, both for its biological properties and for its minerals bioaccessibility value.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma Tumor Progression in Mice

2016 ◽  
Vol 16 (9) ◽  
pp. 1172-1183 ◽  
Author(s):  
Lamia Benguedouar ◽  
Mesbah Lahouel ◽  
Sophie C. Gangloff ◽  
Anne Durlach ◽  
Florent Grange ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Tumour Progression ◽  
Ethanolic Extract ◽  
Complementary Therapy ◽  
Melanoma Cells ◽  
Biological Properties ◽  
Therapeutic Treatment ◽  
Melanoma Tumor ◽  
Ki 67

Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

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