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
Phorbas Sponges
Porifera, commonly referred to as marine sponges, are acknowledged as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention over the years. They are widespread in all continents, and several structurally unique bioactive compounds have been identified from this species. 
  • 769
  • 30 Nov 2021
Topic Review
Mycobacteriophages as Diagnostics
Tuberculosis (TB) is one of the most impactful diseases of the modern era. Current diagnostics are struggling to meet the multifaceted challenges TB presents. Mycobacteriophages (specific phages active against mycobacterial species) are now being utilised to create promising new diagnostic technologies. Here we explore and review contemporary phage diagnostics targeting mycobacteria, while commenting on key areas warranting further investigation and development. 
  • 364
  • 29 Nov 2021
Topic Review
Cardiac Tissue Engineering for Treating Myocardial Infarction
Ischemic heart disease (IHD) causes myocardial infarction (MI), which results in the death and loss of cardiomyocytes (CMs). Apoptosis, necrosis, and autophagy in CMs are the typical hallmarks of cardiac pathology in MI. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic effects of the treatment for MI.
  • 470
  • 29 Nov 2021
Topic Review
Lipid and Polymer-Based siRNA Carriers for Cancer Therapy
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME).
  • 989
  • 26 Nov 2021
Topic Review
Barnase-Barstar Pair in Cancer Research and Nanotechnology
Barnase is an extracellular ribonuclease secreted by Bacillus amyloliquefaciens that was originally studied as a small stable enzyme with robust folding. The identification of barnase intracellular inhibitor barstar led to the discovery of an incredibly strong protein-protein interaction. Together, barnase and barstar provide a fully genetically encoded toxin-antitoxin pair having an extremely low dissociation constant. Moreover, compared to other dimerization systems, the barnase-barstar module provides the exact one-to-one ratio of the complex components and possesses high stability of each component in a complex and high solubility in aqueous solutions without self-aggregation. The unique properties of barnase and barstar allow the application of this pair for the engineering of different variants of targeted anticancer compounds and cytotoxic supramolecular complexes. Using barnase in suicide gene therapy has also found its niche in anticancer therapy.
  • 553
  • 26 Nov 2021
Topic Review
Cancer-Derived Exosomes in Carcinogenesis
The exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. 
  • 553
  • 22 Nov 2021
Topic Review
Alpha-Ketoglutarate and 5-HMF
Clinical and pre-clinical studies of an anti-tumoral solution containing aKG, 5-HMF, N-acetyl-selenomethionine, and N-acetylmethionine for treating tumors showed, on one hand, good therapeutic efficacy during infusion therapy in prostate cancer patients by increasing the PSA doubling time; on the other hand, a reduction of tumoral mass was shown in lung cancer patients.
  • 687
  • 19 Nov 2021
Topic Review
Ursolic Acid in Cancer and Diabetic Neuropathy Diseases
Ursolic acid (UA) is a promising triterpenoid compound present in several plants’ leaves, flowers, and fruits. It shows a broad range of pharmaceutical properties and therapeutic effects. UA has been utilized as a herbal medicine with excellent pharmacological activities.
  • 635
  • 19 Nov 2021
Topic Review
Lipid Nanoparticulate Drug Delivery Systems and Skin Disorders
Lipid nanoparticles (LN) are recognized as promising drug delivery systems (DDS) in treating skin disorders. Solid lipid nanoparticles (SLN) together with nanostructured lipid carriers (NLC) exhibit excellent tolerability as these are produced from physiological and biodegradable lipids. Moreover, LN applied to the skin can improve stability, drug targeting, occlusion, penetration enhancement, and increased skin hydration compared with other drug nanocarriers. Furthermore, the features of LN can be enhanced by inclusion in suitable bases such as creams, ointments, gels (i.e., hydrogel, emulgel, bigel), lotions, etc. 
  • 636
  • 16 Nov 2021
Topic Review
Targeting Engineered Nanoparticles for Breast Cancer Therapy
Breast cancer (BC) is the second most common cancer in women globally after lung cancer. Presently, the most important approach for BC treatment consists of surgery, followed by radiotherapy and chemotherapy. Therapeutic drugs or natural bioactive compounds generally incorporate engineered NPs of ideal sizes and shapes to enhance their solubility, circulatory half-life, and biodistribution, while reducing their side effects and immunogenicity. Furthermore, ligands such as peptides, antibodies, and nucleic acids on the surface of NPs precisely target BC cells. Engineered NPs and their ideal methodology can be validated in the next-generation platform for preventive and therapeutic effects against BC.
  • 517
  • 12 Nov 2021
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