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International Journal of Pharmaceutics Feb 2021Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of... (Review)
Review
Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of antibodies requires special precautions to ensure safety and efficacy of the product. In particular, minimizing antibody product heterogeneity is crucial as drug substance variants may impair the activity, efficacy, safety, and pharmacokinetic properties of an antibody, consequently resulting in the failure of a product in pre-clinical and clinical development. This review will cover the manufacturing and formulation challenges and advances of therapeutic monoclonal antibodies, focusing on improved processes to minimize variants and ensure batch-to-batch consistency. Processes put in place by regulatory agencies, such as Quality-by-Design (QbD) and current Good Manufacturing Practices (cGMP), and how their implementation has aided drug development in pharmaceutical companies will be reviewed. Advances in formulation and considerations on the intended use of a therapeutic antibody, including the route of administration and patient compliance, will be discussed.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cell Line; Humans; Pharmaceutical Preparations
PubMed: 33309833
DOI: 10.1016/j.ijpharm.2020.120164 -
Physical Review. E Feb 2023The morphology and motion behavior of a cell are highly influenced by its external biological, chemical, and physical stimuli, and geometric confinement. In this paper,...
The morphology and motion behavior of a cell are highly influenced by its external biological, chemical, and physical stimuli, and geometric confinement. In this paper, it is revealed that the mean curvature of the substrate significantly influences the adhesion of vesicles. By employing the variational method and investigating the Helfrich free energy, the configuration of axisymmetric vesicles adhered to curved spherical substrates is obtained theoretically. Moreover, numerical simulations based on the finite element method are also carried out to investigate the adhesion of vesicles on curved substrates with complex shapes. It is found that for a fixed area of a vesicle, its total free energy depends mainly on the mean curvature of the adhesion region but is insensitive to the specific shape of the substrate, and the total free energy monotonically decreases with the increase in the mean curvature. In addition, possible biological significances of the curvature-dependent adhesion, such as the shape of the cell and antibiofouling, are discussed. This study may deepen our understanding of the underlying mechanisms of adhesion in cellular activities.
PubMed: 36932565
DOI: 10.1103/PhysRevE.107.024405 -
Carbohydrate Polymers Oct 2023Cellulose has attracted interest from researchers both in academic and industrial sectors due to its unique structural and physicochemical properties. The ease of... (Review)
Review
Cellulose has attracted interest from researchers both in academic and industrial sectors due to its unique structural and physicochemical properties. The ease of surface modification of cellulose by the integration of nanomaterials, magnetic components, metal organic frameworks and polymers has made them a promising adsorbent for solid phase extraction of emerging contaminants, including pharmaceutical residues. This review summarizes, compares, and contrasts different types of cellulose-based adsorbents along with their applications in adsorption, extraction and pre-concentration of pharmaceutical residues in water for subsequent analysis. In addition, a comparison in efficiency of cellulose-based adsorbents and other types of adsorbents that have been used for the extraction of pharmaceuticals in water is presented. From our observation, cellulose-based materials have principally been investigated for the adsorption of pharmaceuticals in water. However, this review aims to shift the focus of researchers to the application of these adsorbents in the effective pre-concentration of pharmaceutical pollutants from water at trace concentrations, for quantification. At the end of the review, the challenges and future perspectives regarding cellulose-based adsorbents are discussed, thus providing an in-depth overview of the current state of the art in cellulose hybrid adsorbents for extraction of pharmaceuticals from water. This is expected to inspire the development of solid phase exraction materials that are efficient, relatively cheap, and prepared in a sustainable way.
Topics: Cellulose; Water; Contrast Media; Solid Phase Extraction; Pharmaceutical Preparations
PubMed: 37479430
DOI: 10.1016/j.carbpol.2023.121097 -
Drug Discovery Today Oct 2022Despite a century of intensive research, there is still a lack of disease-modifying treatments for neurodegenerative diseases that pose a threat to human society. A... (Review)
Review
Despite a century of intensive research, there is still a lack of disease-modifying treatments for neurodegenerative diseases that pose a threat to human society. A well-documented knowledge and resource gap has impeded the translation of fundamental research into promising therapies. In addition, the analysis of extensive preclinical data to allow the improved selection of therapeutic technologies and clinical candidates for further development is challenging. To address this need, we describe technologies that have emerged over the past decade that have enabled the development of novel, high-quality, cost-effective treatments for major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Moreover, we benchmark emerging technologies that have been adopted by top pharmaceutical companies looking to bridge the gap between drug discovery and drug development in neurodegenerative disease.
Topics: Alzheimer Disease; Drug Discovery; Humans; Neurodegenerative Diseases; Parkinson Disease; Pharmaceutical Preparations
PubMed: 35728774
DOI: 10.1016/j.drudis.2022.06.005 -
Physical Review. E Jan 2023The spontaneous emergence of patterns in nature, such as stripes and spots, can be mathematically explained by reaction-diffusion systems. These patterns are often...
The spontaneous emergence of patterns in nature, such as stripes and spots, can be mathematically explained by reaction-diffusion systems. These patterns are often referred as Turing patterns to honor the seminal work of Alan Turing in the early 1950s. With the coming of age of network science, and with its related departure from diffusive nearest-neighbor interactions to long-range links between nodes, additional layers of complexity behind pattern formation have been discovered, including irregular spatiotemporal patterns. Here we investigate the formation of Turing patterns in simplicial complexes, where links no longer connect just pairs of nodes but can connect three or more nodes. Such higher-order interactions are emerging as a new frontier in network science, in particular describing group interaction in various sociological and biological systems, so understanding pattern formation under these conditions is of the utmost importance. We show that a canonical reaction-diffusion system defined over a simplicial complex yields Turing patterns that fundamentally differ from patterns observed in traditional networks. For example, we observe a stable distribution of Turing patterns where the fraction of nodes with reactant concentrations above the equilibrium point is exponentially related to the average degree of 2-simplexes, and we uncover parameter regions where Turing patterns will emerge only under higher-order interactions, but not under pairwise interactions.
PubMed: 36797896
DOI: 10.1103/PhysRevE.107.014216 -
Journal of Medical Systems Mar 2021The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze...
Developing an Integrated Electronic Medication Reconciliation Platform and Evaluating its Effects on Preventing Potential Duplicated Medications and Reducing 30-Day Medication-Related Hospital Revisits for Inpatients.
The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.
Topics: Continuity of Patient Care; Medical Order Entry Systems; Medical Records Systems, Computerized; Medication Errors; Medication Reconciliation; Patient Care Team; Pharmaceutical Preparations; Pharmacy Service, Hospital; Quality Assurance, Health Care; Retrospective Studies; Taiwan
PubMed: 33644834
DOI: 10.1007/s10916-021-01717-8 -
Analytical and Bioanalytical Chemistry Jul 2020The presence of pharmaceuticals, which are considered as contaminants of emerging concern, in natural waters is currently recognized as a widespread problem. Monitoring... (Review)
Review
The presence of pharmaceuticals, which are considered as contaminants of emerging concern, in natural waters is currently recognized as a widespread problem. Monitoring these contaminants in the environment has been an important field of research since their presence can affect the ecosystems even at very low levels. Several analytical techniques have been developed to detect and quantify trace concentrations of these contaminants in the aquatic environment, namely high-performance liquid chromatography, gas chromatography, and capillary electrophoresis, usually coupled to different types of detectors, which need to be complemented with time-consuming and costly sample cleaning and pre-concentration procedures. Generally, the enzyme-linked immunosorbent assay (ELISA), as other immunoassay methodologies, is mostly used in biological samples (most frequently urine and blood). However, during the last years, the number of studies referring the use of ELISA for the analysis of pharmaceuticals in complex environmental samples has been growing. Therefore, this work aims to present an overview of the application of ELISA for screening and quantification of pharmaceuticals in the aquatic environment, namely in water samples and biological tissues. The experimental procedures together with the main advantages and limitations of the assay are addressed, as well as new incomes related with the application of molecular imprinted polymers to mimic antibodies in similar, but alternative, approaches. Graphical Abstract.
Topics: Animals; Aquatic Organisms; Environmental Monitoring; Enzyme-Linked Immunosorbent Assay; Pharmaceutical Preparations; Water; Water Pollutants, Chemical
PubMed: 32088755
DOI: 10.1007/s00216-020-02509-8 -
Drug Testing and Analysis Aug 2023The first nootropic prohibited in sport was fonturacetam (4-phenylpiracetam, carphedon) in 1998. Presented here 25 years later is a broad-scale consideration of the... (Review)
Review
The first nootropic prohibited in sport was fonturacetam (4-phenylpiracetam, carphedon) in 1998. Presented here 25 years later is a broad-scale consideration of the history, pharmacology, prevalence, regulations, and doping potential of nootropics viewed through a lens of 50 selected dietary supplements (DS) marketed as "cognitive enhancement," "brain health," "brain boosters," or "nootropics," with a focus on unauthorized ingredients. Nootropic DS have risen to prominence over the last decade often as multicomponent formulations of bioactive ingredients presenting compelling pharmacological questions and potential public health concerns. Many popular nootropics are unauthorized food or DS ingredients according to the European Commission including huperzine A, yohimbine, and dimethylaminoethanol; unapproved pharmaceuticals like phenibut or emoxypine (mexidol); previously registered drugs like meclofenoxate or reserpine; EU authorized pharmaceuticals like piracetam or vinpocetine; infamous doping agents like methylhexaneamine or dimethylbutylamine; and other investigational substances and peptides. Several are authorized DS ingredients in the United States resulting in significant global variability as to what qualifies as a legal nootropic. Prohibited stimulants or ß2-agonists commonly used in "pre-workout," "weight loss," or "thermogenic" DS such as octodrine, hordenine, or higenamine are often stacked with nootropic substances. While stimulants and ß2-agonists are defined as doping agents by the World Anti-Doping Agency (WADA), many nootropics are not, although some may qualify as non-approved substances or related substances under catch-all language in the WADA Prohibited List. Synergistic combinations, excessive dosing, or recently researched pharmacology may justify listing certain nootropics as doping agents or warrant additional attention in future regulations.
Topics: Nootropic Agents; Prevalence; Central Nervous System Stimulants; Dietary Supplements; Pharmaceutical Preparations; Doping in Sports
PubMed: 37357012
DOI: 10.1002/dta.3529 -
Physical Review. E Dec 2022Perceptual learning (PL) involves long-lasting improvement in perceptual tasks following extensive training and is accompanied by modified neuronal responses in sensory...
Perceptual learning (PL) involves long-lasting improvement in perceptual tasks following extensive training and is accompanied by modified neuronal responses in sensory cortical areas in the brain. Understanding the dynamics of PL and the resultant synaptic changes is important for causally connecting PL to the observed neural plasticity. This is theoretically challenging because learning-related changes are distributed across many stages of the sensory hierarchy. In this paper, we modeled the sensory hierarchy as a deep nonlinear neural network and studied PL of fine discrimination, a common and well-studied paradigm of PL. Using tools from statistical physics, we developed a mean-field theory of the network in the limit of a large number of neurons and large number of examples. Our theory suggests that, in this thermodynamic limit, the input-output function of the network can be exactly mapped to that of a deep linear network, allowing us to characterize the space of solutions for the task. Surprisingly, we found that modifying synaptic weights in the first layer of the hierarchy is both sufficient and necessary for PL. To address the degeneracy of the space of solutions, we postulate that PL dynamics are constrained by a normative minimum perturbation (MP) principle, which favors weight matrices with minimal changes relative to their prelearning values. Interestingly, MP plasticity induces changes to weights and neural representations in all layers of the network, except for the readout weight vector. While weight changes in higher layers are not necessary for learning, they help reduce overall perturbation to the network. In addition, such plasticity can be learned simply through slow learning. We further elucidate the properties of MP changes and compare them against experimental findings. Overall, our statistical mechanics theory of PL provides mechanistic and normative understanding of several important empirical findings of PL.
Topics: Learning; Brain; Neural Networks, Computer; Neuronal Plasticity; Neurons
PubMed: 36671118
DOI: 10.1103/PhysRevE.106.064406 -
Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries.ESMO Open Apr 2023Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer...
BACKGROUND
Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries.
MATERIALS AND METHODS
We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR.
RESULTS
Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company.
CONCLUSIONS
TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.
Topics: Humans; Retrospective Studies; Europe; European Union; Antineoplastic Agents; Pharmaceutical Preparations
PubMed: 37030113
DOI: 10.1016/j.esmoop.2023.101208