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
Heterologous Host for Alternative Production of Amaryllidaceae Alkaloids
Amaryllidaceae alkaloids (AAs) are plant specialized metabolites with therapeutic properties exclusively produced by the Amaryllidaceae plant family. Bioengineered microbial hosts that grow rapidly can produce plant target specialized metabolites faster as compared to whole plant systems. In addition, the production of plant metabolites in heterologous hosts can reduce downstream extraction process, which eventually becomes more economically sustainable. For the successful synthesis of plant metabolites such as AAs, heterologous hosts require the introduction of reconstructed biosynthetic pathway, requiring key enzymes. This requires comprehensive knowledge of the enzymatic reactions involved in the biosynthesis of the compound of interest in the native host organisms (i.e., plants).
  • 1.2K
  • 06 Jul 2022
Topic Review
Mathematical Modeling and Computational Tools in Drug Design
The conventional drug discovery approach is an expensive and time-consuming process, but its limitations have been overcome with the help of mathematical modeling and computational drug design approaches. Previously, finding a small molecular candidate as a drug against a disease was very costly and required a long time to screen a compound against a specific target. The development of novel targets and small molecular candidates against different diseases including emerging and reemerging diseases remains a major concern and necessitates the development of novel therapeutic targets as well as drug candidates as early as possible. In this regard, computational and mathematical modeling approaches for drug development are advantageous due to their fastest predictive ability and cost-effectiveness features. Computer-aided drug design (CADD) techniques utilize different computer programs as well as mathematics formulas to comprehend the interaction of a target and drugs. Traditional methods to determine small-molecule candidates as a drug have several limitations, but CADD utilizes novel methods that require little time and accurately predict a compound against a specific disease with minimal cost.
  • 6.5K
  • 01 Aug 2022
Topic Review
CAR T Cell Locomotion in Solid Tumor Microenvironment
The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). The ability of CAR T cells to efficiently migrate to the tumor site, infiltrate suppressive barriers, and survive the harsh TME represents a crucial prerequisite for carrying out the anti-tumor function.
  • 1.1K
  • 05 Jul 2022
Topic Review
Phenolic Compound Family Extracted from Raspberries
In plant physiology, a phenolic compound family can act as an antioxidant and antimicrobial agent, and their biosynthesis follows the shikimate and phenylpropanoid pathways.
  • 1.6K
  • 04 Jul 2022
Topic Review
Flavonoids-Based Delivery Systems towards Cancer Therapies
Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, is considered a major scourge in low-income countries. Its development is mostly associated with the human papillomavirus persistent infection and despite the availability of preventive vaccines, they are only widely administered in more developed countries, thus leaving a large percentage of unvaccinated women highly susceptible to this type of cancer. The treatments are based on invasive techniques, being far from effective. Therefore, the search for novel, advanced and personalized therapeutic approaches is imperative. Flavonoids belong to a group of natural polyphenolic compounds, well recognized for their great anticancer capacity, thus promising to be incorporated in cancer therapy protocols. However, their use is limited due to their low solubility, stability and bioavailability. Several types of flavonoid-based delivery systems are being developed for anticancer therapy, namely for cervical cancer. The consideration of these new forms of delivery systems allows for the use of fewer flavonoids as well as permits the use of ligands that efficiently target these systems to cancer cells, therefore reducing the risk of toxicity in healthy cells and improving their therapeutic effect. A variety of delivery systems for the encapsulation of these drugs can be explored, depending on the material considered and the properties exhibited by the drug.
  • 939
  • 08 Jul 2022
Topic Review
Role of Microbiomes in Skin Aging
The skin has a multifactorial aging process, caused by both intrinsic and extrinsic factors. A major theory of aging involves cellular senescence or apoptosis resulting from oxidative damage as the skin’s antioxidant system tends to weaken with age. The human microbiota is a complex ecosystem that is made up of microorganisms (bacteria, fungi, and viruses). Both gut and skin microbiota have essential roles in the protection against invading pathogens, mediating inflammatory conditions, and the modulation of the immune system which is involved in both innate and adaptive immune responses. 
  • 2.5K
  • 04 Jul 2022
Topic Review
Chitosans and Nanochitosans
Chitosan displays a dual function, acting as both an active ingredient and/or carrier for pharmaceutical bioactive molecules and metal ions. Its hydroxyl- and amino-reactive groups and acetylation degree can be used to adjust this biopolymer’s physicochemical and pharmacological properties in different forms, including scaffolds, nanoparticles, fibers, sponges, films, and hydrogels, among others. 
  • 1.2K
  • 01 Jul 2022
Topic Review
Green Innovation and Industry and Talent
With increasing pressure on industry resulting from the need for ecological and environmental protection and sustainable development, green innovation development has gradually become a central issue of concern. With predictions of “peak” carbon, the need for carbon neutrality, and the requirement to pursue sustainable development goals, green innovation is not only important for the high-quality growth of the pharmaceutical industry but also represents an impetus to develop high-level talent. The promotion of the further coordination and integration of industry and talent through green innovation is an important issue in contemporary industrial economic development. 
  • 1.1K
  • 01 Jul 2022
Topic Review
Sulfated Galactofucans
Fucoidans encompass versatile and heterogeneous sulfated biopolysaccharides of marine origin, specifically brown algae and marine invertebrates. The reported studies revealed diverse chemical skeletons in which l-fucose is the main sugar monomer. However, other sugars, i.e., galactose, mannose, etc., have been identified to be interspersed, forming several heteropolymers, including galactofucans/fucogalactans (G-fucoidans). Particularly, sulfated galactofucans are associated with rich chemistry contributing to more promising bioactivities than fucans and other marine polysaccharides. The previous reports showed that G-fucoidans derived from Undaria pinnatifida were the most studied; 21 bioactivities were investigated, especially antitumor and antiviral activities, and unique biomedical applications compared to other marine polysaccharides were demonstrated.
  • 893
  • 30 Jun 2022
Topic Review
Antiviral Properties of Seaweeds
Bioactive compounds from seaweed’s currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological activities which are expressed through diverse mechanisms of actions. This research mainly focuses on the antiviral activity of seaweed’s extracts, highlighting the mechanisms of actions of some seaweed molecules against infection caused by different types of enveloped viruses: influenza, Lentivirus (HIV-1), Herpes viruses, and coronaviruses. Seaweed metabolites with antiviral properties can act trough different pathways by increasing the host’s defense system or through targeting and blocking virus replication before it enters host cells. Several studies have already established the large antiviral spectrum of seaweed’s bioactive compounds. 
  • 1.5K
  • 04 Jul 2022
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