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
Protein Translocation to Endosymbiotic Organelles
The problem with increasing the yield of recombinant proteins is resolvable using different approaches, including the transport of a target protein to cell compartments with a low protease activity. In the cell, protein targeting involves short-signal peptide sequences recognized by intracellular protein transport systems. 
  • 1.3K
  • 17 Oct 2022
Topic Review
Anticancer Mechanisms of Natural and Synthetic Chalcones
ATP-binding cassette subfamily G and tubulin pharmacological mechanisms decrease the effectiveness of anticancer drugs by modulating drug absorption and by creating tubulin assembly through polymerization. A series of natural and synthetic chalcones have been reported to have very good anticancer activity, with a half-maximal inhibitory concentration lower than 1 µM. By modulation, it is observed in case of the first mechanism that methoxy substituents on the aromatic cycle of acetophenone residue and substitution of phenyl nucleus by a heterocycle and by methoxy or hydroxyl groups have a positive impact. To inhibit tubulin, compounds bind to colchicine binding site. Presence of methoxy groups, amino groups or heterocyclic substituents increase activity.
  • 1.0K
  • 14 Oct 2022
Topic Review
MDM2-Based Proteolysis-Targeting Chimeras (PROTACs)
Proteolysis-targeting chimeras (PROTACs) are molecules that selectively degrade a protein of interest (POI). The incorporation of ligands that recruit mouse double minute 2 (MDM2) into PROTACs, forming the so-called MDM2-based PROTACs, has shown promise in cancer treatment due to its dual mechanism of action: a PROTAC that recruits MDM2 prevents its binding to p53, resulting not only in the degradation of POI but also in the increase of intracellular levels of the p53 suppressor, with the activation of a whole set of biological processes, such as cell cycle arrest or apoptosis. In addition, these PROTACs, in certain cases, allow for the degradation of the target, with nanomolar potency, in a rapid and sustained manner over time, with less susceptibility to the development of resistance and tolerance, without causing changes in protein expression, and with selectivity to the target, including the respective isoforms or mutations, and to the cell type, overcoming some limitations associated with the use of inhibitors for the same therapeutic target.
  • 2.2K
  • 15 Oct 2022
Topic Review
Silver Nanoparticles for Chronic Wound Management
Infections are the primary cause of death from burns and diabetic wounds. The clinical difficulty of treating wound infections with conventional antibiotics has progressively increased and reached a critical level, necessitating a paradigm change for enhanced chronic wound care. The most prevalent bacterium linked with these infections is Staphylococcus aureus, and the advent of community-associated methicillin-resistant Staphylococcus aureus has posed a substantial therapeutic challenge. Most existing wound dressings are ineffective and suffer from constraints such as insufficient antibacterial activity, toxicity, failure to supply enough moisture to the wound, and poor mechanical performance. Using ineffective wound dressings might prolong the healing process of a wound. To meet this requirement, nanoscale scaffolds with their desirable qualities, which include the potential to distribute bioactive agents, a large surface area, enhanced mechanical capabilities, the ability to imitate the extracellular matrix (ECM), and high porosity, have attracted considerable interest. The incorporation of nanoparticles into nanofiber scaffolds constitutes a novel approach to “nanoparticle dressing” that has acquired significant popularity for wound healing. Due to their remarkable antibacterial capabilities, silver nanoparticles are attractive materials for wound healing. 
  • 3.5K
  • 22 Oct 2022
Topic Review
Pentosan Polysulphate as a Potential Xylan based Prebiotic
In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut–brain, gut–lung and gut–stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols.
  • 1.0K
  • 12 Oct 2022
Topic Review
Applications of Fucoidan from Marine Macroalgae
According to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature system, fucoidan specifically designates the heterogeneous marine sulfated polysaccharides which are copiously found in the cell wall matrix of various species of brown algae. The cell walls of brown algae consist of an amorphous matrix of acid polysaccharides, such as fucoidan and alginic acid, which are linked to each other by proteins, giving structural integrity and flexibility to the seaweed. Generally, fucoidan constitutes about 5–10% of the dry algal biomass, which varies based on the species and the seasons. The fucoidan is used in regenerative medicine, drug delivery systems and the food industry.
  • 2.1K
  • 14 Oct 2022
Topic Review
CRISPR-Cas System for Genetic Disease Therapy
CRISPRs (clusters of regularly inter-spaced palindromic repeats) is a term that refers to regular and repetitive nucleotide sequences that are universally present in bacterial DNA. It was first discovered in 1987 by Professor Nakada’s team at Osaka University in Japan. Since then, several researchers have discovered that this repeating sequence is the microorganism’s defense system for fighting virus invasion. That is, when a microorganism is infected with a bacteria-specific virus, some of the surviving individuals cut part of the virus’s DNA and insert it into their genome one after another. Bacteria defend themselves against phages and plasmids by using the CRISPR-CRISPR-associated protein (Cas) system, which is a genetically encoded RNA-mediated adaptive immunity system. The CRISPR-Cas system is extremely diverse, and it is broadly classified into two classes (I and II), which are further classified into six types (I-VI) and several subtypes. Cascade is the effector complex for CRISPR interference in class I/type I systems. It is composed of CRISPR RNA (crRNA), a large and small Cas subunit, as well as a variable number of Cas5, Cas6, and Cas7 that recognize the target and recruit Cas3, cleaving the target DNA. On the other hand, the RNP surveillance complex in class II systems is made up of a single Cas protein, Cas9 or Cpf1, and this effector complex participates in both target recognition and cleavage.
  • 879
  • 08 Oct 2022
Topic Review
Strategies of Vaccinia Virus in Tumor Virotherapy
Oncolytic virotherapy has emerged as a novel form of cancer immunotherapy. Oncolytic viruses (OVs) can directly infect and lyse the tumor cells, and modulate the beneficial immune microenvironment. Vaccinia virus (VACV) is a promising oncolytic vector because of its high safety, easy gene editing, and tumor intrinsic selectivity. To further improve the safety, tumor-targeting ability, and OV-induced cancer-specific immune activation, various approaches have been used to modify OVs. The recombinant oncolytic VACVs with deleting viral virulence factors and/or arming various therapeutic genes have displayed better therapeutic effects in multiple tumor models. Moreover, the combination of OVs with other cancer immunotherapeutic approaches, such as immune checkpoint inhibitors and CAR-T cells, has the potential to improve the outcome in cancer patients. This will open up new possibilities for the application of OVs in cancer treatment, especially for personalized cancer therapies.
  • 720
  • 30 Sep 2022
Topic Review
Ultrasound-Responsive Nanocarriers for Breast Cancer Chemotherapy
Breast cancer is the most common type of cancer and is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite its ample use, chemotherapy has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target.
  • 1.2K
  • 29 Sep 2022
Topic Review
Molecular Components of Grape Seeds and Grape Marc
Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer.
  • 3.3K
  • 28 Sep 2022
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