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

Paclitaxel and Breast Cancer

Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer (BC). Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure. Factors contributing to PTX resistance, such as ABC transporters, microRNAs (miRNAs), or mutations in certain genes, along with side effects of PTX including peripheral neuropathy or hypersensitivity associated with the vehicle used to overcome its poor solubility, are responsible for intensive research concerning the use of PTX in preclinical and clinical studies. Novelties such as albumin-bound PTX (nab-PTX) demonstrate a progressive approach leading to higher efficiency and decreased risk of side effects after drug administration. Moreover, PTX nanoparticles for targeted treatment of BC promise a stable and efficient therapeutic intervention.

528
05 Aug 2021

Topic Review

Antitumor Action of Mango Peel

Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. Ethanolic extracts from Mangifera indica L. have been proved to possess anti-tumor properties in many cancer systems. However, although most effects have been demonstrated with fruit pulp extract, the underlying molecular mechanisms of mango peel are still unclear. This research was undertaken to explore the effects of mango peel extract (MPE) on colon cancer cell lines. Data obtained demonstrated that MPE can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. A consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage- was observed. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane (VDAC1, mitofilin, and some members of Bcl-2 family) —with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.

827
04 Aug 2021

Topic Review

Cyclodextrin Multicomponent Complexes: Pharmaceutical Applications

Cyclodextrins (CD) are a family of macromolecules obtained by enzymatic degradation of starch. Their structure resembles a truncated cone, with a somewhat lipophilic central cavity and an external hydrophilic surface. Due to these characteristics the pharmaceutical applications are mostly related to the ability of CDs to form inclusion complexes, formed by interactions between guest (drug) and host (CD) molecules, and they have the ability to modulate several properties positively affecting the performances and therapeutic profiles of drugs. Besides, a drug–CD complex with the addition of an auxiliary substance, that are called multicomponent or ternary complex, can have a synergic effect, allowing the use of low concentrations of the host compounds, thereby optimizing the cost, toxicity and formulation volume in the final product. Also, these additives such as amino acids, organic acids and bases, and water-soluble polymers interacting with CDs can modulate in vitro and in vivo drug dissolution, thereby modifying the drug’s pharmacokinetic profile.

482
30 Aug 2021

Topic Review

Euphorbia

Euphorbia genus (Euphorbiaceae family), which is the third largest genus of angiosperm plants comprising ca. 2000 recognized species, is used all over the world in traditional medicine, especially in the traditional Chinese medicine. Members of this taxa are promptly recognizable by their specialized inflorescences and latex. In this review, an overview of Euphorbia-derived natural products such as essential oils, extracts, and pure compounds, active in a broad range of biological activities, and with potential usages in health maintenance, is described. The chemical composition of essential oils from Euphorbia species revealed the presence of more than 80 phytochemicals, mainly oxygenated sesquiterpenes and sesquiterpenes hydrocarbons, while Euphorbia extracts contain secondary metabolites such as sesquiterpenes, diterpenes, sterols, flavonoids, and other polyphenols.

1.3K
26 Jul 2021

Topic Review

Microbes’ Roles in Wound Healing

Normal wound healing cascade is highly dynamic and has four distinct overlapping phases which involves several cellular and molecular interactions. It is known to be one of the most complicated processes in human body. The wound healing mechanism can be interrupted due to the involvement of several diseases that eventually develop to chronic wounds such as in diabetic foot ulcers. Infection is a common problem in chronic wound cause by microbes residing on the superficial layer of the skin. It is frequently resulting in impaired wound healing and patient morbidity and mortality. Antibiotic therapy and wound dressings are the main treatments to treat infected chronic wounds. However, the presence of polymicrobial infections, formation of bacterial biofilms and antibiotics resistance are the major challenges faced by healthcare providers to kill or eliminate the microbes from the wounds. Considering all the possible factors, more studies are needed to elucidate the role of microbes as well as the selection of suitable empirical antibiotics in reducing the infections and provide optimal healing in chronic wounds.

1.0K
23 Jul 2021

Topic Review

Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration

The treatment of dairy cows with nonsteroidal drugs is applied experimentally to investigate the relevance of inflammation during the periparturient period. Despite appearing healthy, dairy cows throughout the transition period and mainly after parturition can develop a pro-inflammatory status that may negatively influence milk production and cows’ health. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated to have both positive or negative effects on health and milk production, depending on the type of inhibition mechanism, the dose administered and the cows’ lactation numbers. At present, the safety and efficacy of NSAIDs have not been irrefutably demonstrated; therefore, their use to improve metabolic and inflammatory status, as well as milk production and cow health after parturition, should be carefully evaluated.

453
21 Jul 2021

Topic Review

Lysophosphatidic Acid and Cancer

Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis.

546
14 Jul 2021

Topic Review

Phytocannabinoids Biosynthesis in Plants

Phytocannabinoids are a structurally diverse class of bioactive naturally occurring compounds found in angiosperms, fungi, and liverworts and produced in several plant organs such as the flower and glandular trichrome of Cannabis sativa, the scales in Rhododendron, and oil bodies of liverworts such as Radula species; they show a diverse role in humans and plants. Moreover, phytocannabinoids are prenylated polyketides, i.e., terpenophenolics, which are derived from isoprenoid and fatty acid precursors. Additionally, targeted productions of active phytocannabinoids have beneficial properties via the genes involved and their expression in a heterologous host. Bioactive compounds show a remarkable non-hallucinogenic biological property that is determined by the variable nature of the side chain and prenyl group defined by the enzymes involved in their biosynthesis. Phytocannabinoids possess therapeutic, antibacterial, and antimicrobial properties; thus, they are used in treating several human diseases.

712
14 Jul 2021

Topic Review

Nanotechnology-facilitated Bacterial Therapy

In recent years, advancing nanotechnology has extended bacterial therapies to a higher level through tailoring bacteria on a nanoscale, such as bacteria-derived nanovesicles and bacterial membrane-coated nanoparticles, or endowing bacteria with abilities to serve as drug carriers, photosensitizers, and sonosensitizers.

739
09 Jul 2021

Topic Review

Bisphosphonate-Based Conjugates and Derivatives

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited because of severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the dominant class of drugs used to inhibit metastatic bone cancer. It is also used to treat osteoporosis and other bone diseases. However, bisphosphonate also suffers from serious side effects. Thus, there is a serious need to develop bisphosphonate conjugates with promising therapeutic outcomes for treating metastatic bone cancer and osteoporosis. This review article focuses on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.

485
09 Jul 2021

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