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
Umbilical Cord Blood-Derived sEV
Small extracellular vesicles (sEV) are a group of particles of nanometric size, released by virtually all cells. These vesicles function as biologic messengers, carrying proteins, lipids and nucleic acids as a form of paracrine cellular communication. Umbilical cord blood (UCB) is a priviledged source of sEV, due to its abundance in naïve cells with strong regenerative and immunomodulatory potential. Hence, UCB-derived sEV can be exploited for their therapeutic properties, taking advantage of nature's tools for achieving homeostasis.
  • 551
  • 29 Sep 2021
Topic Review
Novel Delivery Systems of Polyphenols
Polyphenols encapsulated in liposomes are known to produce more substantial effects on targeted cells than unencapsulated polyphenols, while having minimal cytotoxicity in healthy cells. 
  • 1.1K
  • 29 Sep 2021
Topic Review
NK Cells for Adoptive Immunotherapy
NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challanges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technology advancements in gene delivery, gene editing and chimeric antigen receptor (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable 'off-the-shelf' products with fewer side effects. The recent advanced in NK cell biology along with current approaches for potentiating NK cell proliferation and activity was highlighted, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy.
  • 540
  • 27 Sep 2021
Topic Review
Limosilactobacillus reuteri Fermented Brown Rice
Oxidative stress has been postulated to play a role in several diseases, including cardiovascular diseases, diabetes, and stress-related disorders (anxiety/depression). Presently, natural plant-derived phytochemicals are an important tool in reducing metabolomic disorders or for avoiding the side effects of current medicinal therapies. Brown Rice (Oryza sativa L.) is an important part of Asian diets reported as a rich source of bioactive phytonutrients. 
  • 529
  • 26 Sep 2021
Topic Review
Oral Sulfated Fucose-Rich Polysaccharides
Sulfated fucose-rich polysaccharides from marine organisms are unique molecules with various pharmacological effects. They might have promising therapeutic applications in different diseases.
  • 677
  • 24 Sep 2021
Topic Review
Natural Phenols
Phenols are widespread in nature, being the major components of several plants and essential oils. Natural phenols’ anti-microbial, anti-bacterial, anti-oxidant, pharmacological and nutritional properties are, nowadays, well established. Hence, given their peculiar biological role, numerous studies are currently ongoing to overcome their limitations, as well as to enhance their activity.
  • 3.2K
  • 29 Sep 2021
Topic Review
Carotenoids of Capsicum Fruits
Pepper of the Capsicum species is a common ingredient in various food preparations by different cultures worldwide. The Capsicum is recognised by its five main domesticated species, namely Capsicum annuum, C. baccatum, C. chinense, C. frutescens and C. pubescens. The genetic diversity in Capsicum offers fruits in wide ranges of morphology and carotenoid profile. Carotenoids enhance the value of pepper from a nutritional standpoint, despite being commonly prized for the pharmacologically active pungent capsaicinoids. Carotenoids of pepper comprise mainly of the unique, powerful and highly stable capsanthin and capsoroubin, together with β-carotene, β-cryptoxanthin, lutein, zeaxanthin, antheraxanthin and violaxanthin. These carotenoids are present at diverse profile and varying levels, biosynthetically connected to the fruit maturity stages.
  • 555
  • 16 Sep 2021
Topic Review
Unnatural Gallotannins
Nature has been a source of inspiration for the development of new pharmaceutically active agents. Polyphenols, including gallotannins, are widely studied as they protect cells against oxidative damage and pathogen attack. A series of new unnatural gallotannins (GTs), derived from D-lyxose, D-ribose, D-rhamnose, D-mannose, and D-fructose have been designed and synthesized i order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. Apart from spectral analysis, their antioxidant activity was evaluated. Structurally different GTs were screened in vitro for their antimicrobial properties against a spectrum of staphylococci, enterococci, and mycobacteria. Furthermore, the antibiofilm activity of GTs against S. aureus, and their ability to inhibit sortase A were inspected. Experimental data suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, and food industry applications.
  • 648
  • 14 Sep 2021
Topic Review
CAMs in Peripheral Nerve Regeneration
Despite the progressive advances, current standards of treatments for peripheral nerve injury do not guarantee complete recovery. Thus, alternative therapeutic interventions should be considered. Complementary and alternative medicines (CAMs) are widely explored for their therapeutic value, but their potential use in peripheral nerve regeneration is underappreciated. Various CAMs enhanced proliferation and migration of Schwann cells in vitro, primarily through activation of MAPK pathway and FGF-2 signaling, respectively. Animal studies demonstrated the ability of CAMs to promote peripheral nerve regeneration and functional recovery, which are partially associated with modulations of neurotrophic factors, pro-inflammatory cytokines, and anti-apoptotic signaling. 
  • 513
  • 15 Sep 2021
Topic Review
Topical Insulin Delivery
Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. 
  • 721
  • 13 Sep 2021
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