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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Topic Review
Targeting N-Linked Glycosylation Pathways for Gestational Diabetes Mellitus
Gestational diabetes mellitus (GDM) is a common pregnancy complication that affects approximately 10% of pregnant women worldwide. While current treatments for GDM focus on managing blood glucose levels through diet, exercise, and medication, there is a need for new therapeutic strategies that can target the underlying molecular mechanisms of the disease. Recent research has shown that alterations in N-linked glycosylation pathways may play a role in the development of GDM. In this study, we used both the STRING and KEGG pathway databases to analyze protein-protein interactions and pathways involved in N-linked glycosylation. Our analysis identified several potential therapeutic targets for GDM, including fructosyltransferase 8 (FUT8) and N-acetylglucosaminyltransferase III (GnT-III), which have been shown to improve insulin sensitivity and glucose tolerance in animal models of diabetes. Targeting N-linked glycosylation pathways may represent a novel therapeutic strategy for GDM, and further research is needed to explore the potential of this approach.
  • 13
  • 03 Jun 2023
Topic Review
Nutritional Value of Bee Pollen
BP’s richness in nutrients, such as proteins, vitamins, minerals, oligo-elements, and unsaturated fatty acids, is certain, along with the fact that it provides a moderate calorie intake as well as a good level of tolerance and safety, except for in the case of allergic reactions or external pollution, which remain manageable and predictable.
  • 12
  • 02 Jun 2023
Topic Review
Principles of pH-Responsive Drug Delivery
The paradigm of drug carriers’ usage to overcome the non-specific distribution of therapeutic agents in the body, including chemotherapeutic substances that exert severe toxic stress on healthy tissues, has been actively developed. One of the main pillars of this paradigm is the increased or even selective accumulation of drug delivery systems (DDSs) carrying therapeutic agents in tumor interstitium harnessing the differences between normal and cancer tissues properties. Thus, structural features of tumors, such as hypervascularization, vascular pathologies, and impaired functionality of lymphatic drainage, can be utilized to differentiate tumors from healthy tissues and selectively accumulate drug carriers. In particular, tumor-surrounding vessels are characterized by defects in the endothelial layer lining the blood vessel wall, represented by wide fenestrations (up to several microns) and other features that lead to an increase in the permeability of this barrier for small objects, making the effective extravasation of nanosized carriers from the bloodstream to tumor interstitium possible. Methods of selective therapy via the systemic administration of therapeutic agents based on increased permeability of the tumor vessels’ wall, known under the general name of the EPR effect, have become widespread and have inspired the creation of a large number of vehicles proposed for the delivery of chemotherapeutic agents. In summary, the EPR effect implies the extravasation of nanosized drug carriers through endothelial fenestra and their retention in the interstitial volume of the tumor due to dysfunctional lymphatic drainage.
  • 34
  • 01 Jun 2023
Topic Review
Molecular Mechanisms of Cancer Immunotherapy
The cancer-immunity cycle is characterized by various stimulatory and inhibitory factors, which together regulate the immune response and halt the extreme response that may lead to autoimmune disease. Immunotherapy of cancer has rejuvenated the field of tumor immunology and revolutionized treatment options.
  • 35
  • 30 May 2023
Topic Review
Plasma Clearance Receptors of FVIII and VWF
Congenital deficiency in blood coagulation factor (F) VIII (FVIII) results in excessive bleeding. The disease (hemophilia A) is treated with infusions of therapeutic FVIII concentrates, either plasma-derived (pdFVIII) or produced with recombinant DNA technology (rFVIII). Due to the relatively short FVIII plasma half-life (~12 h), such treatment requires frequent FVIII infusions (3–4 per week in prophylaxis) that calls for developing more efficient longer-acting FVIII products, in particular with an extended plasma lifetime, commonly termed half-life (EHL). Relevant protein modifications are performed via genetic and/or chemical modification of rFVIII, and efficient designs require understanding the molecular mechanisms of FVIII plasma clearance.
  • 49
  • 29 May 2023
Topic Review
Chemically Modified Electrodes for the Detection of Antidepressants
Major depressive disorder is a widespread condition with antidepressants as the main pharmacological treatment. However, some patients experience concerning adverse reactions or have an inadequate response to treatment. Analytical chromatographic techniques, among other techniques, are valuable tools for investigating medication complications, including those associated with antidepressants. Nevertheless, there is a growing need to address the limitations associated with these techniques. In recent years, electrochemical (bio)sensors have garnered significant attention due to their lower cost, portability, and precision. Electrochemical (bio)sensors can be used for various applications related to depression, such as monitoring the levels of antidepressants in biological and in environmental samples. They can provide accurate and rapid results, which could facilitate personalized treatment and improve patient outcomes. This state-of-the-art literature review aims to explore the latest advancements in the electrochemical detection of antidepressants.
  • 33
  • 25 May 2023
Topic Review
Tuberculosis in the Twenty-First Century
With an estimated two billion people being carriers of latent tuberculosis infection (LTBI), the gains achieved by increasing access to diagnostics and treatment, although substantial, have had a modest impact on the global burden of tuberculosis (TB). At the same time, increased access to treatment has had the unintended consequence that drug-resistant TB (DR-TB) has increased dramatically. Earlier TB control strategies strongly emphasizing medical treatment have failed to address these issues effectively.
  • 39
  • 23 May 2023
Topic Review
Affibody- and DARPin-Conjugated Nanomaterials in Cancer Therapy
Affibodies and designed ankyrin repeat proteins (DARPins) are synthetic proteins originally derived from the Staphylococcus aureus virulence factor protein A and the human ankyrin repeat proteins, respectively. The use of these molecules in healthcare has been recently proposed as they are endowed with biochemical and biophysical features heavily demanded to target and fight diseases, as they have a strong binding affinity, solubility, small size, multiple functionalization sites, biocompatibility, and are easy to produce; furthermore, impressive chemical and thermal stability can be achieved, especially when using affibodies. In this sense, several examples reporting on affibodies and DARPins conjugated to nanomaterials have been published, demonstrating their suitability and feasibility in nanomedicine for cancer therapy.
  • 44
  • 22 May 2023
Topic Review
Janus Particles
Janus particles have emerged as a novel and smart material that could improve pharmaceutical formulation, drug delivery, and theranostics. Janus particles have two distinct compartments that differ in functionality, physicochemical properties, and morphological characteristics, among other conventional particles.
  • 43
  • 18 May 2023
Topic Review
Plant-Derived Nanoparticles for Prostate Cancer Therapy
Plants have demonstrated potential in providing various types of phytomedicines with chemopreventive properties that can combat prostate cancer. However, despite their promising in vitro activity, the incorporation of these phytochemicals into the market as anticancer agents has been hindered by their poor bioavailability, mainly due to their inadequate aqueous solubility, chemical instability, and unsatisfactory circulation time. To overcome these drawbacks, it has been suggested that the incorporation of phytochemicals as nanoparticles can offer a solution. The use of plant-based chemicals can also improve the biocompatibility of the formulated nanoparticles by avoiding the use of certain hazardous chemicals in the synthesis, leading to decreased toxicity in vivo. Moreover, in some cases, phytochemicals can act as targeting agents to tumour sites. 
  • 48
  • 18 May 2023
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