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
Important Plant Viruses for Plant Biotechnology
Plant viruses have traditionally been studied as pathogens in the context of understanding the molecular and cellular mechanisms of a particular disease affecting crops. In recent years, viruses have emerged as a new alternative for producing biological nanomaterials and chimeric vaccines. Plant viruses were also used to generate highly efficient expression vectors, revolutionizing plant molecular farming (PMF). 
  • 639
  • 18 Jan 2023
Topic Review
Mechanisms of Bortezomib Resistance in Multiple Myeloma Cell
Bortezomib is the most effective chemotherapeutic drug used in the treatment of MM. This inhibitor is a dipeptide boronic acid analogue discovered in 1995 and is the premier in the class of chymotrypsin-like (CP) inhibitors. Bortezomib is a C-terminal boronic acid, and the boron atom is essential for inhibiting the proteasome activity because of its ability to specifically and tightly bind the β5 catalytic subunit. Boronates form tetrahedral adducts, which are further stabilized by a hydrogen bond between the N-terminal amino group of threonines and the hydroxyl groups of boronic acid. These bonds provide a higher influence for Bortezomib than other drugs developed for inhibition. It binds the proteasome with a high resolution, slowly dissociates, and provides a stable but reversible proteasome inhibition. Various mechanisms have been suggested to explain the multidrug resistance in cancer cells. Increased drug excretion, decreased drug uptake, activation of detoxification systems, inhibition of apoptosis, alterations in cell cycle regulation factors, and changes in drug targets are among the causes.
  • 633
  • 17 Jan 2023
Topic Review
Antibiotic Bacterial Resistance
Antibiotics are the main treatment against bacterial infections in animals and plants. As explained before, efficacy loss is known as antibiotic resistance; this manifestation occurs when bacteria mutate in response to excess and sublethal doses of these drugs. Antibiotic resistance is usually classified into intrinsic and acquired resistance. The first one is constitutive of each species, which means that each generation will present it. In contrast, the acquired mechanism occurs when bacteria obtain resistance genes through conjugation, transformation, transduction, and transposition. Regardless of the type of resistance, both cause this problem.
  • 403
  • 18 Jan 2023
Topic Review
Different Phenotypes of Immune Infiltrates
Besides the mere count of lymphocytic infiltration, the phenotype of the lymphocytes may also dictate the clinical outcome of HER2-positive breast cancer patients, as every specific subset has a specific role in cancer development. Cumulative data from human studies have associated the different immune populations with a predominant contribution to either pro- or antitumor activities.
  • 404
  • 17 Jan 2023
Topic Review
Auricularia auricula’s Separation and Purification
Auricularia auricula polysaccharides (AAP) have been widely studied in the field of medicine and healthcare because of their unique structure and physiological activity. Many species of Auricularia auricula polysaccharides have been extracted, isolated, and purified by different methods, and their structures have been analyzed. Auricularia auricula polysaccharides have been proven to have beneficial effects on the human body, including slowing the aging process, controlling the intestinal system, and treating cardiovascular disorders.
  • 674
  • 19 Jan 2023
Topic Review
Intervertebral Disc Tissue Engineering with Additive Manufacturing
Intervertebral disc (IVD) degeneration is one of the major causes of lower back pain, a common health condition that greatly affects the quality of life. With an increasing elderly population and changes in lifestyle, there exists a high demand for novel treatment strategies for damaged IVDs. Researchers have investigated IVD tissue engineering (TE) as a way to restore biological and mechanical functions by regenerating or replacing damaged discs using scaffolds with suitable cells. These scaffolds can be constructed using material extrusion additive manufacturing (AM), a technique used to build three-dimensional (3D), custom discs utilising computer-aided design (CAD). Structural geometry can be controlled via the manipulation of printing parameters, material selection, temperature, and various other processing parameters
  • 390
  • 12 Jan 2023
Topic Review
Effects of Whole-Cell and Acellular Pertussis Vaccines
After the pertussis vaccine had been introduced in the 1940s and was shown to be very successful in reducing the morbidity and mortality associated with the disease, the possibility of improving both vaccine composition and vaccination schedules has become the subject of continuous interest.
  • 554
  • 13 Jan 2023
Topic Review
Skin-Derived ABCB5+ Mesenchymal Stem Cells for Inflammatory Diseases
The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency.
  • 442
  • 10 Jan 2023
Topic Review
Targeting Post-Translational Modifications in Lung Cancer
Lung cancer is one of the most common cancers worldwide. It consists of two different subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite novel therapeutic options such as immunotherapy, only 20% of lung cancer patients survive the disease after five years. This low survival rate is due to acquired drug resistance and severe off-target effects caused by currently used therapies. Identification and development of novel and targeted therapeutic approaches are urgently required to improve the standard of care for lung cancer patients.
  • 663
  • 09 Jan 2023
Topic Review
Antioxidant Effects of Lycopene
Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. 
  • 490
  • 09 Jan 2023
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