Biopharmaceuticals Technology | Encyclopedia MDPI

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

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.

4.9K
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.

2.0K
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.

1.2K
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.

1.1K
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.

1.2K
13 Sep 2021

Topic Review

Peptide-Assisted Nucleic Acid Delivery Systems

Advances in peptide development have made peptide-assisted gene delivery more efficient in vitro and, in some instances, in small animal models. For example, cell and tissue selectivity could be greatly enhanced in the newest generation of CPPs. Other advances which allow for improved performance with regard to targeting and delivery of nucleic acids include adapting peptide sequences to facilitate escape or release from intracellular vesicles or respond to environmental stimuli for a controlled release of cargo, and the development of composite, multivalent peptide-based, or peptide-coupled structures.

1.1K
08 Sep 2021

Topic Review

Enzyme Therapy

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.

2.5K
06 Sep 2021

Topic Review

CYP3A4

CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions.

4.7K
01 Sep 2021

Topic Review

Punicalagin in Cancer Prevention

Punicalagin, present in pomegranate, myrobalan, yellow wood, tropical almond, and pink rock-rose, belongs to ellagitannins - a subgroup of hydrolyzable tannins. In vitro studies, based on cell line experiments, have demonstrated punicalagin anti-cancer actions on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types. Punicalagin seems to work through a redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence or autophagy (thus compromising neoplastic progression). However, since it readily undergoes hydrolysis releasing e.g. ellagic acid, these might be its products which are responsible for the observed effects. Moreover, when practical application of punicalagin in chemoprevention is addressed, its biotransformation in the human organism should be considered (including both host and microbiome enzymatic impact). Therefore, however promising punicalagin antineoplastic properties seem to be, in vivo-based research should be conducted before translating the results obtained from in vitro studies into practice.

1.6K
26 Aug 2021

Topic Review

Antibacterial Secondary Metabolites from Basidiomycetes

Fungi are a rich source of secondary metabolites with several pharmacological activities such as antifungal, antioxidant, antibacterial and anticancer to name a few. Due to the large number of diverse structured chemical compounds they produce, fungi from the phyla Ascomycota, Basidiomycota and Muccoromycota have been intensively studied for isolation of bioactive compounds. Basidiomycetes-derived secondary metabolites are known as a promising source of antibacterial compounds with activity against Gram-positive bacteria. The continued emergence of antimicrobial resistance (AMR) poses a major challenge to patient health as it leads to higher morbidity and mortality, higher hospital-stay duration and substantial economic burden in global healthcare sector. One of the key culprits for AMR crisis is Staphylococcus aureus causing community-acquired infections as the pathogen develops resistance towards multiple antibiotics. The recent emergence of community strains of S. aureus harbouring methicillin-resistant (MRSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) genes associated with increased virulence is challenging. Despite the few significant developments in antibiotic research, successful MRSA therapeutic options are still needed to reduce the use of scanty and expensive second-line treatments. This paper provides an overview of findings from various studies on antibacterial secondary metabolites from basidiomycetes, with a special focus on antistaphylococcal activity.

1.5K
20 Aug 2021

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