Summary

The advent of biopharmaceuticals in current medicine brought enormous benefits to the treatment of life-threatening human diseases (e.g., cancer, diabetes and neurodegenerative disorders), and improved the well-being of many people worldwide. The global portfolio of these therapeutic products include proteins and antibodies, nucleic acids, and cell-based products, and continues to expand at a rapid pace - approvals in the period 2015-2018 essentially double the typical five-yearly historical approval pace (G. Walsh, Nat. Biotechnol., 36:1136-1145, 2018) -, representing a significant share of the entire market of pharmaceuticals.

Innovation in the (bio)pharmaceutical industry has been driven towards the development of cost-effective manufacturing processes, envisaging the delivery of products in high quantity, with superior quality (purity), and high specificity, with the ultimate goal of benefiting patients. Progress in this direction have resulted from the application of novel technologies in the upstream stage (high-throughput, single-use devices, statistical optimization of media and fermentation conditions, QbD, and continuous processing), while at the downstream level, chromatography has evolved through the development of new resins and ligands, coupled with advances in process modelling, operating and control strategies.

An emerging trend is the application of alternative solvents such as ionic liquids and deep eutectic solvents, in which their structure and physicochemical properties can be tuned to address unmet needs in (bio)pharmaceutical research. These compounds may be derived from natural and reneawable sources and hold great promise in the development of efficient, sustainable and cost-effective biopharmaceuticals purification processes.

This Entry Collection aims to provide the latest progresses achieved in pharmaceuticals bioprocessing. We welcome submissions of original research, comprehensive reviews and perspectives, including, but not limited, to the following fields:

- Upstream processing (genetic engineering, systems biology, difficult-to-express proteins, expression conditions, Quality by Design approaches, process analytical technologies);

- Chromatographic purification methods (process modelling and control, continuous bioprocessing, design and characterization of resins and ligands, new formats);

- Alternative purification methods (aqueous biphasic systems, filtration, crystallization, precipitation);

- Application of neoteric solvents in upstream and downstream stages;

- Analytical characterization of biopharmaceuticals (stability, post-translational modifications, biological activity, immunogenicity); 

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Entries
Topic Review
Glycomimetic Peptides as Therapeutic Tools for Skin Diseases
The entry of peptides into glycobiology has led to the development of a unique class of therapeutic tools. Although numerous and well-known peptides are active as endocrine regulatory factors that bind to specific receptors, and peptides have been used extensively as epitopes for vaccine production, the use of peptides that mimic sugars as ligands of lectin-type receptors has opened a unique approach to modulate activity of immune cells. Ground-breaking work that initiated the use of peptides as tools for therapy identified sugar mimetics by screening phage display libraries. The peptides that have been discovered show significant potential as high-avidity, therapeutic tools when synthesized as multivalent structures.
  • 931
  • 22 Feb 2023
Topic Review
Toxicological Risks of the Cobalt–Chromium Alloys in Dentistry
Cobalt–chromium (Co-Cr) alloys have been used for a long period of time in dentistry, but several risk factors remain involved. The toxicological risk of Co-Cr dental alloys is actually a sensitive subject with the European regulatory changes, namely regulation (EU) 2017/745 and annex VI to the CLP regulation (EC) 1972/2008. Studies assessing Co-Cr dental alloys’ biocompatibility are urgently needed.
  • 4.9K
  • 22 Feb 2023
Topic Review
Peculiarities of Tumor Cell Metabolism for Cancer Treatment
In tumor cells, ketolysis “via” succinyl-CoA: 3-oxoacid-CoAtransferase (SCOT) and acetyl-CoA acetyltransferase 1 (ACAT1) is a major source of mitochondrial acetyl-CoA. Active ACAT1 tetramers stabilize by tyrosine phosphorylation, which facilitates the SCOT reaction and ketolysis. Tyrosine phosphorylation of pyruvate kinase PK M2 has the opposite effect, stabilizing inactive dimers, while pyruvate dehydrogenase (PDH), which is already inhibited by phosphorylation, is acetylated by ACAT1 and is doubly locked. This closes the glycolytic supply of acetyl-CoA. In addition, since tumor cells must synthesize fatty acids to create new membranes, they automatically turn off the degradation of fatty acids into acetyl-CoA (“via” the malonyl-CoA brake for the fatty acid carnityl transporter). Thus, inhibiting SCOT the specific ketolytic enzyme and ACAT1 should hold back tumor progression. However, tumor cells are still able to take up external acetate and convert it into acetyl-CoA in their cytosol “via” an acetyl-CoA synthetase, which feeds the lipogenic pathway; additionally, inhibiting this enzyme would make it difficult for tumor cells to form new lipid membrane and survive.
  • 11.5K
  • 21 Feb 2023
Topic Review
Blood–Brain Barrier for CNS Drug Delivery
Blood Brain Barrier is a diffusional interface between the brain tissue and the blood vasculature. 
  • 1.7K
  • 22 Feb 2023
Topic Review
Chasing Uterine Cancer with NK Cell-Based Immunotherapies
Gynecological cancers, including endometrial adenocarcinoma, significantly contribute to cancer incidence and mortality worldwide. The immune system plays a significant role in endometrial cancer pathogenesis. (uterine) NK cells, a component of innate immunity, are among the critical innate immune cells in the uterus crucial in menstruation, embryonic development, and fighting infections. NK cell number and function influence endometrial cancer development and progression. Hence, it becomes crucial to understand the role of local (uterine) NK cells in uterine cancer.
  • 888
  • 20 Feb 2023
Topic Review
Virus-Like Particles for TEM Regulation against Cancer
Tumor development and metastasis are intimately associated with the tumor microenvironment (TME), and it is difficult for vector-restricted drugs to act on the TME for long-term cancer immunotherapy. Virus-like particles (VLPs) are nanocage structures self-assembled from nucleic acid free viral proteins. Most VLPs range from 20–200 nm in diameter and can naturally drain into lymph nodes to induce robust humoral immunity. As natural nucleic acid nanocarriers, their surfaces can also be genetically or chemically modified to achieve functions such as TME targeting. 
  • 896
  • 17 Feb 2023
Topic Review
Pleiotropic Anticancer of Withaferin A
Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins.
  • 1.6K
  • 16 Feb 2023
Topic Review
Anti-Obesity Effects of Natural Constituents
Obesity is a chronic metabolic complication, and its management requires long-term medication, lifestyle modifications, and dietary interventions. Patients taking anti-obesity medications may suffer from side effects such as psychiatric disorders, anxiety, depression, and vitamin deficiency. Various classes of natural compounds are promising agents to combat the obesity pandemic. Developing safer drugs may require polytherapeutic strategies to combat the global obesity pandemic.
  • 1.1K
  • 14 Feb 2023
Topic Review
Hallmarks and Significance of Apoptosis
Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. 
  • 6.9K
  • 14 Feb 2023
Topic Review
Drug Delivery Technologies for mRNA Vaccines
mRNA vaccine molecules are large (104–106 Da) in size and are negatively charged. They are unable to pass through the lipid bilayer of cell membranes. Naked mRNA would be destroyed and degraded by the nucleases present in the bloodstream. In addition, naked mRNA is also attached and engulfed by immune cells in the tissue and the serum. Methods to deliver mRNA molecules into the cells include techniques such as gene gun, electroporation, and ex vivo transfection. The in vivo methods of delivering mRNA involves transfection of immune or non-immune cells using lipids or transfecting agents.
  • 1.8K
  • 13 Feb 2023
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