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
Topical and Intradermal Administration in Horse
Horses are companion animals with temperamental and sensitive characteristics that play an important role in the lives of many individuals. Therefore, the global demand and market for equine healthcare products are rapidly increasing. However, comprehensive, and intensive information on drug development relating to equine health is still very much in its infancy. Delivering drugs to horses orally is a major challenge, as the physiology and anatomy of the equine gastro-intestinal tract (GIT) can result in poor bioavailability of some oral drugs. Additionally, due to their size, the dosages required are much larger and higher cost compared to those of humans; with potential of adverse effects, especially for antibiotics, following the administration of some drugs.
  • 1.0K
  • 28 Jan 2023
Topic Review
Chromatin and Cancer
A hallmark of cancers is uncontrolled cell proliferation, frequently associated with an underlying imbalance in gene expression. This transcriptional dysregulation observed in cancers is multifaceted and involves chromosomal rearrangements, chimeric transcription factors, or altered epigenetic marks. Traditionally, chromatin dysregulation in cancers has been considered a downstream effect of driver mutations. Disruption of this large-scale chromatin in proliferating cancerous cells in conventional chemotherapies induces DNA damage and provides a positive feedback loop for chromatin rearrangements and tumor diversification. Consequently, the surviving cells from these chemotherapies become tolerant to higher doses of the therapeutic reagents, which are significantly toxic to normal cells. Furthermore, the disorganization of chromatin induced by these therapies accentuates nuclear fragility, thereby increasing the invasive potential of these tumors.
  • 985
  • 29 Jan 2023
Topic Review
Bionanomaterials Based on Honey and Propolis for wounds
Wound healing is a public health concern worldwide, particularly in chronic wounds due to delayed healing and susceptibility to bacterial infection. Nanomaterials are widely used in wound healing treatments due to their unique properties associated with their size and very large surface-area-to-volume ratio compared to the same material in bulk. The properties of nanomaterials can be expanded and improved upon with the addition of honey and propolis, due to the presence of bioactive molecules such as polyphenols, flavonoids, peptides, and enzymes. These bionanomaterials can act at different stages of wound healing and through different mechanisms, including anti-inflammatory, antimicrobial, antioxidant, collagen synthesis stimulation, cell proliferation, and angiogenic effects.
  • 1.5K
  • 29 Jan 2023
Topic Review
Artificial Intelligence in Fluorescent Nanodiamonds Biomedical Imaging
The ability to precisely monitor the intracellular temperature directly contributes to the essential understanding of biological metabolism, intracellular signaling, thermogenesis, and respiration. The intracellular heat generation and its measurement can also assist in the prediction of the pathogenesis of chronic diseases. Intracellular thermometry without altering the biochemical reactions and cellular membrane damage is challenging, requiring appropriately biocompatible, nontoxic, and efficient biosensors. Bright, photostable, and functionalized fluorescent nanodiamonds (FNDs) have emerged as excellent probes for intracellular thermometry and magnetometry with the spatial resolution on a nanometer scale. The temperature and magnetic field-dependent luminescence of naturally occurring defects in diamonds are key to high-sensitivity biosensing applications. Alterations in the surface chemistry of FNDs and conjugation with polymer, metallic, and magnetic nanoparticles have opened vast possibilities for drug delivery, diagnosis, nanomedicine, and magnetic hyperthermia. The possibilities and outcomes of using AI strategies recommended for early stage disease diagnosis and imaging are discuessed. 
  • 1.1K
  • 18 Jan 2023
Topic Review
Structure and Physicochemical Properties of Konjac Glucomannan
Konjac glucomannan (KGM), can not only be applied as a food additive, which greatly improves the taste and flavor of food and extends the shelf life of food but also occupies an important role in T2DM (Type 2 Diabetes Mellitus). KGM can extend gastric emptying time, increase satiety, and promote liver glycogen synthesis, and also has the potential to improve intestinal flora and the metabolic system through a variety of molecular pathways in order to positively regulate oxidative stress and immune inflammation, and protect the liver and kidneys.
  • 2.5K
  • 01 Feb 2023
Topic Review
Curcumin-Based Nanomedicines and Neurodegenerative Diseases
Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Neurodegenerative diseases (ND) are brain disorders characterized mainly by progressive loss of selectivity in vulnerable populations of neurons, which contrasts with metabolic or toxic brain disorders due to the select static neuronal loss that occurs in these. Theoretically, ND can be classified according to primary clinical signals such as dementia, motor neuron disease or parkinsonism, anatomic distribution of neurodegeneration such as frontotemporal degenerations, extrapyramidal disorders or spinocerebellar degenerations or, principally, ND can be classified as their molecular abnormality.
  • 981
  • 18 Jan 2023
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). 
  • 1.6K
  • 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.
  • 1.7K
  • 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.
  • 919
  • 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.
  • 833
  • 17 Jan 2023
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