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
Electrochemical Glucose Sensors Based on 2D Materials
Diabetes is a health disorder that necessitates constant blood glucose monitoring. The industry is always interested in creating novel glucose sensor devices because of the great demand for low-cost, quick, and precise means of monitoring blood glucose levels. Electrochemical glucose sensors, among others, have been developed and are now frequently used in clinical research. Nonetheless, despite the substantial obstacles, these electrochemical glucose sensors face numerous challenges. Because of their excellent stability, vast surface area, and low cost, various types of 2D materials have been employed to produce enzymatic and nonenzymatic glucose sensing applications. 
  • 799
  • 11 Jul 2022
Topic Review
Nutritional Imbalance in Mechanically Ventilated Multiple Trauma Patients
The critically ill polytrauma patient is characterized by a series of metabolic changes induced by inflammation, oxidative stress, sepsis, and primary trauma, as well as associated secondary injuries associated. Metabolic and nutritional dysfunction in the critically ill patient is a complex series of imbalances of biochemical and genetic pathways, as well as the interconnection between them. Therefore, the equation changes in comparison to other critical patients or to healthy individuals, in which cases, mathematical equations can be successfully used to predict the energy requirements. Recent studies have shown that indirect calorimetry is one of the most accurate methods for determining the energy requirements in intubated and mechanically ventilated patients. Current research is oriented towards an individualized therapy depending on the energy consumption (kcal/day) of each patient that also takes into account the clinical dynamics. By using indirect calorimetry, one can measure, in real time, both oxygen consumption and carbon dioxide production. Energy requirements (kcal/day) and the respiratory quotient (RQ) can be determined in real time by integrating these dynamic parameters into electronic algorithms. In this manner, nutritional therapy becomes personalized and caters to the patients’ individual needs, helping patients receive the energy substrates they need at each clinically specific time of treatment.
  • 431
  • 11 Jul 2022
Topic Review
MicroRNA Expression in Sepsis
A critically ill polytrauma patient is one of the most complex cases to be admitted to the intensive care unit, due to both the primary traumatic complications and the secondary post-traumatic interactions. From a molecular, genetic, and epigenetic point of view, numerous biochemical interactions are responsible for the deterioration of the clinical status of a patient, and increased mortality rates. From a molecular viewpoint, microRNAs are one of the most complex macromolecular systems due to the numerous modular reactions and interactions that they are involved in. Regarding the expression and activity of microRNAs in sepsis, their usefulness has reached new levels of significance. MicroRNAs can be used both as an early biomarker for sepsis, and as a therapeutic target because of their ability to block the complex reactions involved in the initiation, maintenance, and augmentation of the clinical status.
  • 438
  • 11 Jul 2022
Topic Review
Ferroptosis Modulation as Therapeutic Target for Glioblastoma Treatment
Glioblastoma multiforme is a lethal disease and represents the most common and severe type of glioma. Drug resistance and the evasion of cell death are the main characteristics of its malignancy, leading to a high percentage of disease recurrence and the patients’ low survival rate. Exploiting the modulation of cell death mechanisms could be an important strategy to prevent tumor development and reverse the high mortality and morbidity rates in glioblastoma patients. Ferroptosis is a recently described type of cell death, which is characterized by iron accumulation, high levels of polyunsaturated fatty acid (PUFA)-containing phospholipids, and deficiency in lipid peroxidation repair. Several studies have demonstrated that ferroptosis has a potential role in cancer treatment and could be a promising approach for glioblastoma patients.
  • 410
  • 08 Jul 2022
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).
  • 481
  • 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.
  • 3.9K
  • 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.
  • 429
  • 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.
  • 680
  • 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.
  • 471
  • 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. 
  • 1.1K
  • 04 Jul 2022
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