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

Cell-Scaffold Constructs for Bone Regeneration Therapy

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration.

1.4K
28 Oct 2021

Topic Review

Role of PARP in TNBC

Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer.

1.2K
29 Oct 2021

Topic Review

ANO1 in Cystic Fibrosis

Cystic fibrosis (CF) is the most common of rare hereditary diseases in Caucasians, and it is estimated to affect 75,000 patients globally. CF is a complex disease due to the multiplicity of mutations found in the CF transmembrane conductance regulator (CFTR) gene causing the CFTR protein to become dysfunctional. Although CFTR is the main chloride channel in the lungs, others could, e.g., anoctamin-1 (ANO1 or TMEM16A), compensate for the deficiency of CFTR.

1.7K
26 Oct 2021

Topic Review

Safety Evaluation of Nanotechnology Products

Nanomaterials are now being used in a wide variety of biomedical applications. Medical and health-related issues, however, have raised major concerns, in view of the potential risks of these materials against tissue, cells, and/or organs and these are still poorly understood. These particles are able to interact with the body in countless ways, and they can cause unexpected and hazardous toxicities, especially at cellular levels. Therefore, undertaking in vitro and in vivo experiments is vital to establish their toxicity with natural tissues.

924
25 Oct 2021

Topic Review

Novel Characterization in Radiopharmaceutical Preclinical Design

In this entry, the potential of a digital autoradiography system equipped with a super resolution screen has been evaluated to investigate the biodistribution of a 18F-PSMA inhibitor in a prostate cancer mouse model. Twelve double xenograft NOD/SCID mice (LNCAP and PC3 tumours) were divided into three groups according to post-injection time points of an 18F-PSMA inhibitor. Groups of 4 mice were used to evaluate the biodistribution of the radiopharmaceutical after 30-, 60- and 120-min post-injection. Data here reported demonstrated that the digital autoradiography system is suitable to analyse the biodistribution of an 18F-PSMA inhibitor in both whole small-animal bodies and in single organs. The exposure of both whole mouse bodies and organs on the super resolution screen surface allowed the radioactivity of the PSMA inhibitor distributed in the tissues to be detected and quantified. Data obtained by using a digital autoradiography system were in line with the values detected by the activity calibrator. In addition, the image obtained from the super resolution screen allowed a perfect overlap with the tumour images achieved under the optical microscope. In conclusion, biodistribution studies performed by the autoradiography system allow the microscopical modifications induced by therapeutic radiopharmaceuticals to be studied by comparing the molecular imaging and histopathological data at the sub-cellular level.

926
22 Oct 2021

Topic Review

Potentiality of Nanoenzymes for Cancer Treatment

Nanozyme synthesis is an innovative technology since it connects nanoparticles with biological activities and framework. Various assays have been implemented for the enzymes of proteins that also implement nanozymes, which could also have the potential for performing the catalysis of similar substrates. Due to such different functions of nanozymes, they are used for the treatment of the environment, biosensing, agents that act against microbes, cytoprotection of different cell biomolecules with management, diagnosis of diseases, etc..

1.1K
22 Oct 2021

Topic Review

Biomedical Applications of Plant-Mediated Zinc Oxide Nanoparticles

Zinc oxide nanoparticles have become one of the most popular metal oxide nanoparticles and recently emerged as a promising potential candidate in the fields of optical, electrical, food packaging, and biomedical applications due to their biocompatibility, low toxicity, and low cost. They have a role in cell apoptosis, as they trigger excessive reactive oxygen species (ROS) formation and release zinc ions (Zn2+) that induce cell death. The zinc oxide nanoparticles synthesized using the plant extracts appear to be simple, safer, sustainable, and more environmentally friendly compared to the physical and chemical routes. These biosynthesized nanoparticles possess strong biological activities and are in use for various biological applications in several industries. Initially, the present review discusses the synthesis and recent advances of zinc oxide nanoparticles from plant sources (such as leaves, stems, bark, roots, rhizomes, fruits, flowers, and seeds) and their biomedical applications (such as antimicrobial, antioxidant, antidiabetic, anticancer, anti-inflammatory, photocatalytic, wound healing, and drug delivery), followed by their mechanisms of action involved in detail.

2.0K
21 Oct 2021

Topic Review

3D Printing in Pharmaceutical Application

Advances in three-dimensional (3D) printing techniques and the development of tailored biomaterials have facilitated the precise fabrication of biological components and complex 3D geometrics over the past few decades. Moreover, the notable growth of 3D printing has facilitated pharmaceutical applications, enabling the development of customized drug screening and drug delivery systems for individual patients, breaking away from conventional approaches that primarily rely on transgenic animal experiments and mass production.

1.2K
25 Jan 2022

Topic Review

Protein Analysis of Gene Mutations in Conjunctival Melanoma

Genetics is the basis of many neoplasms, including conjunctival melanoma (CM). Here, we analyzed five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN and investigated structures of BRAF, NRAS, c-KIT, and PTEN generated with AlphaFold, and NF1 structure from the Protein Databank (PDB). The Predictor of Natural Disordered Protein Regions (PONDR®), the web server for the prediction of intrinsically unstructured regions of proteins (IUPred), and the mean disorder profile (MDP) were utilized to analyze each protein for intrinsically disordered protein regions (IDPRs). AlphaFold and PDB structures show the presence of IDPRs in all five proteins. The bioinformatics analysis confirmed high levels of disorder in these proteins, with most disordered being BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value < 1.0 × 10−16). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

980
21 Oct 2021

Topic Review

Mevalonate Kinase Deficiency and Squalene Synthase Inhibitor (TAK-475)

Mevalonate Kinase Deficiency (MKD) is a rare inborn disease belonging to the family of periodic fever syndromes. The MKD phenotype is characterized by systemic inflammation involving multiple organs, including the nervous system. Current anti-inflammatory approaches to MKD are only partially effective and do not act specifically on neural inflammation. According to the new emerging pharmacology trends, the repositioning of drugs from the indication for which they were originally intended to another one can make mechanistic-based medications easily available to treat rare diseases. According to this perspective, the squalene synthase inhibitor Lapaquistat (TAK-475), originally developed as a cholesterol-lowering drug, might find a new indication in MKD, by modulating the mevalonate cholesterol pathway, increasing the availability of anti-inflammatory isoprenoid intermediates.

1.2K
19 Oct 2021

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