scholarly journals “Biosimilar” generic version of biologic products?

2021 ◽  
Vol 2 (2) ◽  
pp. 114-120
Author(s):  
Muhammad Taher ◽  
◽  
Siti Syazwani Shaari ◽  
Deny Susanti ◽  
Keyword(s):  
Generic Version ◽  
Inflammatory Diseases ◽  
Generic Drugs ◽  
Complex Structure ◽  
In Vivo Studies ◽  
Patient Access ◽  
Expiry Date

Biosimilars are currently popular after the expiry date of patents for biological reference products have expired or soon will expire. Besides, this ‘copycat’ version of biologic products offers much lower costs as compared to the reference products, thus promoting better patient access to the treatment of certain diseases such as cancer, inflammatory diseases, skin disorders and diabetes. This review aims to determine the differences between biosimilars and generic drugs and highlight some issues related to biosimilar products such as comparability, interchangeability, immunogenicity, extrapolation of indication, current legislation, pharmacovigilance, and naming system. Scientific sources from PubMed, Google Scholar, ScienceDirect, and Elsevier were accessed for preparation of this review article. Biosimilars are not generic drugs as they have larger and complex structure as compared to the generic drugs. Due to that, biosimilars are highly similar but not identical to the reference products. Many regulatory authorities have authorized biosimilars under a distinct regulatory process from that of the generic drugs and subjected them to comprehensive comparability studies with their reference products (analytical, nonclinical in vitro, and in vivo studies and clinical trials). Additional evidence from interchangeability studies, extrapolation of indication studies, immunogenicity profile assessments, and pharmacovigilance studies are also beneficial to assess the efficacy, safety, and quality of the biosimilar before and/or after receiving their regulatory approval. Biosimilars are different from generic drugs due to their complexity in structure and manufacturing process. More comprehensive studies are required to ensure their benefits is outweigh the risks.

scholarly journals Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

2021 ◽  
Author(s):  
Bogna Grygiel-Górniak
Keyword(s):  
Connective Tissue ◽  
Viral Infections ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Antiviral Drugs ◽  
In Vivo Studies ◽  
Viral Diseases ◽  
Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

scholarly journals Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

2021 ◽  
Vol 11 (5) ◽  
pp. 336
Author(s):  
Mohammed Ghiboub ◽  
Ahmed M. I. Elfiky ◽  
Menno P. J. de Winther ◽  
Nicola R. Harker ◽  
David F. Tough ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Domain Specific ◽  
Recent Advances ◽  
Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

Novel Self-Micro Emulsifying Drug Delivery System for safe intra muscular delivery with improved pharmacodynamics and pharmacokinetics

2021 ◽  
Vol 18 ◽  
Author(s):  
Subheet Kumar Jain ◽  
Neha Panchal ◽  
Amrinder Singh ◽  
Shubham Thakur ◽  
Navid Reza Shahtaghi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Inflammatory Diseases ◽  
Diclofenac Sodium ◽  
Physical Stability ◽  
In Vivo Studies ◽  
High Concentration

Background: Diclofenac sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20 % w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements resulted in the formulation of an aqueous based injectable but that too used benzyl alcohol reported to be toxic for human use. Objective: To develop an injectable self-micro emulsifying drug delivery system (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Further, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2 % after 4 h, compared to 77±1.6 % inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. Conclusion: The above findings confirmed that liquid SMEDDS could be a successful carrier for the safe and effective delivery of DS

Advancements in Cancer Therapeutics

2021 ◽  
pp. 89-115
Author(s):  
Serda Kecel Gunduz ◽  
Bilge Bicak ◽  
Aysen E. Ozel
Keyword(s):  
Protein Design ◽  
Complex Structure ◽  
Cancer Therapeutics ◽  
New Drugs ◽  
In Vivo Studies ◽  
Drug Induced ◽  
Dimensional Simulation ◽  
Dynamics And Function

In this chapter, computational approaches for the discovery of new drugs that are useful for diagnosis and treatment of disease will be described in three parts. MD technique uniquely supports protein design attempts by giving information about protein dynamics associated with atomic-level descriptions of the relationship between dynamics and function. The purpose of molecular docking is to provide an estimate of the ligand-receptor complex structure using computational methods. By this estimation, the mechanism of drug binding and action are described by determining the three-dimensional simulation of drug and drug-induced macrostructure. ADME characteristics are physicochemically significant descriptors and pharmacokinetically relevant properties used to design more effective drugs and new analogs. As a result, in-silico calculations can provide robust preliminary information as to drug activity and mechanism in the drug production process, as well as in vitro and in vivo studies.

scholarly journals Resistin Is Increased in Periodontal Cells and Tissues: In Vitro and In Vivo Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Andressa V. B. Nogueira ◽  
Marjan Nokhbehsaim ◽  
Sema Tekin ◽  
Rafael S. de Molon ◽  
Luis C. Spolidorio ◽  
...  
Keyword(s):  
Bone Loss ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Male Rats ◽  
In Vivo Studies ◽  
Hard Tissue ◽  
Tissue Metabolism ◽  
Inflammatory Stimuli

Resistin, a proinflammatory adipokine, is elevated in many inflammatory diseases. However, little is known about its performance in periodontitis. The present study is aimed at evaluating resistin expression and synthesis in periodontal cells and tissues under inflammatory/microbial stress in addition to its effects on the periodontium. In vivo, 24 male rats were randomly divided into two groups: control and ligature-induced periodontal disease. After 6 and 12 days, animals were sacrificed to analyze gene expression of adipokines, bone loss, inflammation, and resistin synthesis. In vitro, human periodontal ligament (PDL) fibroblasts were used to evaluate the expression of resistin after inflammatory stimuli. In addition, PDL fibroblasts were exposed to resistin to evaluate its role on soft and hard tissue metabolism markers. The periodontitis group demonstrated significant bone loss, an increase in the number of inflammatory cells and vascular structures, an increase in resistin expression and synthesis, and a decrease in the expression of adiponectin, leptin, and its functional receptor. PDL fibroblasts showed a significant increase in resistin expression and synthesis in response to the inflammatory stimulus by IL-1β. Resistin induced an increase in cytokine expression and a decrease in the regulation of some hard tissue and matrix formation genes in PDL fibroblasts. These data indicate that resistin is produced by periodontal cells and tissues, and this effect is enhanced by inflammatory stimuli. Moreover, resistin seems to interfere with soft and hard tissue metabolism during periodontitis by reducing markers related to matrix formation and bone tissue.

scholarly journals Targeting Wnt/β-Catenin Pathway for Developing Therapies for Hair Loss

2020 ◽  
Vol 21 (14) ◽  
pp. 4915 ◽  
Author(s):  
Bu Young Choi
Keyword(s):  
Hair Loss ◽  
Hair Growth ◽  
In Vivo Studies ◽  
Intracellular Targets ◽  
Remarkable Progress ◽  
Made In

Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis of hair loss and identifying valid intracellular targets for designing effective therapies for hair loss treatment. Whereas a variety of growth factors and signaling pathways have been implicated in hair cycling process, the activation of Wnt/β-catenin signaling plays a central role in hair follicle regeneration. Several plant-derived chemicals have been reported to promote hair growth by activating Wnt/β-catenin signaling in various in vitro and in vivo studies. This mini-review sheds light on the role of Wnt/β-catenin in promoting hair growth and the current progress in designing hair loss therapies by targeting this signaling pathway.

scholarly journals Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 429-437 ◽  
Author(s):  
Rong L. He ◽  
Jian Zhou ◽  
Crystal Z. Hanson ◽  
Jia Chen ◽  
Ni Cheng ◽  
...  
Keyword(s):  
Serum Amyloid A ◽  
Inflammatory Diseases ◽  
Serum Amyloid ◽  
Proteinase K ◽  
In Vivo Studies ◽  
Toll Like Receptor ◽  
Amyloid A ◽  
Toll Like Receptor 2

Abstract The acute-phase protein serum amyloid A (SAA) is commonly considered a marker for inflammatory diseases; however, its precise role in inflammation and infection, which often result in neutrophilia, remains ambiguous. In this study, we demonstrate that SAA is a potent endogenous stimulator of granulocyte colony-stimulated factor (G-CSF), a principal cytokine-regulating granulocytosis. This effect of SAA is dependent on Toll-like receptor 2 (TLR2). Our data demonstrate that, in mouse macrophages, both G-CSF mRNA and protein were significantly increased after SAA stimulation. The induction of G-CSF was blocked by an anti-TLR2 antibody and markedly decreased in the TLR2-deficient macrophages. SAA stimulation results in the activation of nuclear factor–κB and binding activity to the CK-1 element of the G-CSF promoter region. In vitro reconstitution experiments also support that TLR2 mediates SAA-induced G-CSF expression. In addition, SAA-induced secretion of G-CSF was sensitive to heat and proteinase K treatment, yet insensitive to polymyxin B treatment, indicating that the induction is a direct effect of SAA. Finally, our in vivo studies confirmed that SAA treatment results in a significant increase in plasma G-CSF and neutrophilia, whereas these responses are ablated in G-CSF– or TLR2-deficient mice.

scholarly journals Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6238
Author(s):  
Paromita Sarbadhikary ◽  
Blassan P. George ◽  
Heidi Abrahamse
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
In Vivo Studies ◽  
Inflammasome Activation ◽  
Inflammatory Disorders ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

scholarly journals The Effect of Processing Methods on Phytochemical Composition in Bergamot Juice

Foods ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 474 ◽  
Author(s):  
Domenico Cautela ◽  
Filomena Monica Vella ◽  
Bruna Laratta
Keyword(s):  
Antioxidant Activity ◽  
Epidemiological Studies ◽  
Screw Press ◽  
In Vivo Studies ◽  
Press Method ◽  
Citrus Juices ◽  
Processing Techniques

Experimental and epidemiological studies show a positive relation between consumption of citrus juices and reduction of risk for some chronic disorders, such as diabetes and cardiovascular diseases. In particular, the bergamot juice is characterized by noticeable amounts of phytochemicals such as flavanone glycosides, limonoids, and quaternary ammonium compounds, all health-beneficial biomolecules. In vitro and in vivo studies have shown anti-inflammatory, cholesterol-lowering, and anti-diabetic activities attributed to these compounds depending on their chemical structure. However, nutritional content of bergamot juice may vary as consequence of different processing techniques, thus needing to address this claim. For this reason, the objective of this research was to evaluate the effects of different processing systems on the proximate constituents, the composition, and the antioxidant activity of the correspondent juices. Overall, the results indicate that the process employed may influence the chemical composition and the functional properties of the ended juice. Screw press method produced a juice with greater content of flavanone glycosides (ranged from 37 to 402 mg/L) and limonoid aglycones (ranged from 65 to 67 mg/L) than the other processes (p < 0.001). However, the process used for extraction of bergamot juice did not affect significantly the N,N-dimethyl-L-proline content (p < 0.5). Moreover, the screw press juice showed the highest antioxidant activity with EC50 value of 9.35 µg/mL, thus suggesting that this method maintains for health the nutritional quality of a fresh-pressed juice.

scholarly journals Physicochemical, Sensory, and Cooking Qualities of Pasta Enriched with Oat β-Glucans, Xanthan Gum, and Vital Gluten

Foods ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1412 ◽  
Author(s):  
Ada Krawęcka ◽  
Aldona Sobota ◽  
Emilia Sykut-Domańska
Keyword(s):  
Xanthan Gum ◽  
Dry Matter ◽  
Nutritional Value ◽  
Sensory Quality ◽  
Water Solubility ◽  
In Vivo Studies ◽  
Sensory Qualities

The functional properties of β-glucans derived from oats and barley are confirmed by numerous in vitro and in vivo studies. This study aimed to assess the effect of adding 0, 5, 10, 15, and 20% oat (1,3)(1,4)-β-D-glucans to physicochemical properties, as well as the cooking and sensory qualities of durum wheat pasta. Additionally, to improve the cooking and sensory qualities of pasta, we added 5% of xanthan gum and vital gluten. The present study showed that the addition of β-glucans led to an increase of the water absorption index (WAI), water solubility index (WSI), and viscosity of products. At the same time, an increase in the content of fat, ash, and dietary fiber was observed. The addition of (1,3)(1,4)-β-D-glucans influenced the cooking quality of the pasta, extending the minimum cooking time and increasing the loss of dry matter. At the same time, the color of the product changed. In the case of cooked pasta, the addition of β-glucans decreased the brightness and increased the yellowness and redness. It was found that the products enriched with 10–15% of β-glucans, as well as 5% of xanthan gum and vital gluten would yield functional pasta that may offer health benefits beyond its nutritional value. Further, this could influence high cooking and sensory quality.

Sign in / Sign up

Export Citation Format

Share Document