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
Structure-Based Virtual Screening
Molecular docking plays a significant role in early-stage drug discovery, from structure-based virtual screening (VS) to hit-to-lead optimization. VS is a computational approach used to identify chemical structures that are predicted to have particular properties. In drug discovery, it involves computationally searching large libraries of chemical structures to identify those structures that are most likely to bind to a target protein.
  • 3.2K
  • 04 Aug 2022
Topic Review
Bovine Respiratory Disease
Bovine Respiratory Disease is considered one of the most common diseases within the Australian beef industry. During the transitioning period of young cattle going into the feedlot system they experience multiple stressors such as environmental changes, dehydration, and fatigue. These stressors negatively impact on the animals’ overall health by markedly increasing physiological stress and decreasing immune response making them more susceptible to diseases, such as bovine respiratory disease complex (BRD).
  • 1.6K
  • 01 Aug 2022
Topic Review
Phytochemical and Potential Properties of Seaweeds
Seaweeds have been employed as source of highly bioactive secondary metabolites that could act as key medicinal components. Seaweeds have many uses: they are consumed as fodder, and have been used in medicines, cosmetics, energy, fertilizers, and industrial agar and alginate biosynthesis. The beneficial effects of seaweed are mostly due to the presence of minerals, vitamins, phenols, polysaccharides, and sterols, as well as several other bioactive compounds. These compounds seem to have antioxidant, anti-inflammatory, anti-cancer, antimicrobial, and anti-diabetic activities.
  • 2.2K
  • 01 Aug 2022
Topic Review
Evaluation of Biological Activity of Natural Compounds
Natural compounds have diverse structures and are present in different forms of life. Metabolites such as tannins, anthocyanins, and alkaloids, among others, serve as a defense mechanism in live organisms and are undoubtedly compounds of interest for the food, cosmetic, and pharmaceutical industries.
  • 1.1K
  • 01 Aug 2022
Topic Review
Precision Anti-Cancer Medicines by Oligonucleotide in Clinical Reasearch
Oligonucleotide therapeutics enable a direct targeting of the gene by acting at the level of the RNA or at the level of the DNA, based on the Watson-Crick complementary rule of binding.
  • 1.1K
  • 29 Jul 2022
Topic Review
Poly(N-isopropylacrylamide)-Based Hydrogels
Poly(N-isopropylacrylamide) (PNIPAM) is a widely utilized negative thermosensitive polymer (as it has increased solubility with lowering of temperature, causing volume phase transition by forming hydrogen bonds) that has currently sparkled a lot of scientific inquisitiveness. Smart hydrogels based on PNIPAM demonstrate distinct thermoresponsive features close to a lower critical solution temperature (LCST) that enhance their capability in various biomedical applications such as drug delivery, tissue engineering, and wound dressings.
  • 5.7K
  • 29 Jul 2022
Topic Review
Accum™ Technology
Compromised activity is a common impediment for biologics requiring endosome trafficking into target cells. In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or subsequently pumped extracellularly, leading to a reduction in intracellular accumulation. In subsets of dendritic cells (DCs), endosome-engulfed antigens face non-specific proteolysis and collateral damage to epitope immunogenicity before proteasomal processing and subsequent surface presentation. Accum™ is a novel biotechnology exemplifying, in its initial concept, the need to circumvent the biological challenges of ADCs.
  • 1.4K
  • 29 Jul 2022
Topic Review
Stem Cell-Derived Extracellular Vesicles in Bone Defects
The repair of critical bone defects is a hotspot of orthopedic research. With the development of bone tissue engineering (BTE), there is increasing evidence showing that the combined application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes, with hydrogels, scaffolds, and other bioactive materials has made great progress, exhibiting a good potential for bone regeneration. 
  • 786
  • 29 Jul 2022
Topic Review
Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies
Chronic spontaneous urticaria (CSU) considerably alters patients’ quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. 
  • 2.2K
  • 27 Jul 2022
Topic Review
Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy
Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.
  • 1.2K
  • 01 Aug 2022
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