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
Pain Relief for Livestock Husbandry Procedures
A livestock pain relief innovation in Australia in 2005 that led to an awakening of on-farm pain welfare management, was the development of a ‘spray and stay’ topical anaesthesia and antiseptic wound formulation (TAF; Tri-Solfen®, Medical Ethics, Australia) for use during mulesing in sheep. This product, when applied to wounds, rapidly alleviates pain through blockage of nociception, ablates hyperalgesia, minimises bleeding and provides antisepsis with reduced need for antimicrobial cover during healing. With a rapid onset and prolonged duration, the readily observable clinical efficacy commenced a transformational ‘welfare revolution’ in Australian livestock agricultural attitudes and practices with over 120million animals now treated. On application, the TAF forms a long-lasting bio-compatible barrier over the wound, creating its own intrinsic analgesic properties and diminishing the risk of biofilm formation. The TAF acts as a slow-release carrier for the actives, including the two local anaesthetics, lidocaine hydrochloride (5% w/w) and bupivacaine hydrochloride (0.5% w/w), the antiseptic cetrimide (0.5% w/w), in addition to the vasoconstrictor adrenaline acid tartrate (0.00451% w/w) that minimise vasodilation and bleeding, preventing systemic absorption and risk of toxicity. The TAF keeps the actives in contact with the wound tissue, creating synergies that prolong the analgesia well beyond the expected duration of action of actives (at least 24 h) and hastening both healing of husbandry wounds and other lesions, especially those induced by epidermal viral infections including Foot-and-Mouth Disease virus.
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  • 02 Oct 2022
Topic Review
Enzyme Crosslinking Approaches for Bone Tissue Engineering
Crosslinking strategies have been extensively explored in order to design novel hydrogels for bone tissue engineering. Lately, the fabrication of hydrogels with the help of enzyme-mediated crosslinking approaches has been extensively explored. This approach has resulted in promising outcomes with convincing prospects. Enzymes are required in minimal quantity and are very efficient in their actions, as they increase the reaction rate without being expended during the course of the reaction process. The efficiency of an enzyme is defined by the number of substrate molecules converted into products per unit of enzyme, which is also known as turnover number (k cat). The high efficiency of enzyme-based reactions comes from the precise specificity, which ensures the conversion of a particular type of substrate to products. So far, many enzymes have been explored in order to prepare biomimetic hydrogels for bone tissue engineering. The details of every enzyme-based crosslinking approach are discussed in the following sections.
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  • 01 Oct 2022
Topic Review
Applications of Fucoidan
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.
  • 15
  • 30 Sep 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.
  • 23
  • 30 Sep 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.
  • 19
  • 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.
  • 24
  • 29 Sep 2022
Santosh Kumar Sahu
Behuria, H. G., Biswal, B. K. & Sahu, S. K. (2020) Electroformation of liposomes and phytosomes using copper electrode, Journal of Liposome Research, DOI:, Print ISSN: 0898-2104 Online ISSN: 1532-2394 Behuria, H. G. and Sahu, S.K., An anti-microbial terpenoid fraction from Gymnema sylvestre induces flip-flop of fluorescent-phospholipid analogs
  • 18
  • 28 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.
  • 27
  • 28 Sep 2022
Topic Review
Combination Strategies of Different Antimicrobials
Despite the discovery and development of an array of antimicrobial agents, multidrug resistance poses a major threat to public health and progressively increases mortality. The use of antimicrobial agents in combination can produce synergistic effects if each drug invades a different target or signaling pathway with a different mechanism of action. Therefore, drug combinations can achieve a higher probability and selectivity of therapeutic responses than single drugs.
  • 20
  • 28 Sep 2022
Topic Review
Pharmacological Aspects of Moringa oleifera
Moringa oleifera is an ancient remedy plant, known as the miraculous plant due to its many prominent uses and significant health benefits. It is a nutrient-rich plant, with exceptional bioactive compounds, such as polyphenols that possess several medicinal properties. Many significant studies have been carried out to evaluate the ethnomedicinal and pharmacological properties of M. oleifera in various applications.
  • 30
  • 27 Sep 2022
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