Pharmaceutical Industry Research Articles

Advances in Biocatalysis for Sustainable Pharmaceutical Synthesis: Applications, Technological Progress, and Future Directions

Biocatalysis has emerged as a critical tool in pharmaceutical synthesis, offering a range of significant advancements in recent years. This paper provides a comprehensive review of biocatalysis applications in drug synthesis, emphasizing its role in enhancing the efficiency and environmental sustainability of producing complex pharmaceutical molecules. Through detailed case studies, including the biocatalytic synthesis of amoxicillin, paclitaxel, and ribavirin, the paper illustrates the superior reaction efficiency, selectivity, and reduced environmental impact achievable through biocatalysis. The technological advancements discussed include optimizing enzyme activity via genetic engineering, enhancing enzyme stability through covalent modification, and applying enzyme immobilization techniques. Furthermore, the integration of biocatalysis with green chemistry principles is explored, highlighting its potential to reduce harmful byproducts and energy consumption in industrial processes. The paper also delves into the future directions and challenges of scaling biocatalysis for broader industrial application. As an integral part of green chemistry, biocatalysis is poised to play a pivotal role in promoting sustainable development and minimizing environmental impact in the pharmaceutical industry.

A headspace GC-MS method to quantify nitrosamine impurities and precursors in drug products: Method validation and product testing.

Pharmaceutical manufacturers are working to mitigate the formation of nitrosamine impurities in drug products. The work herein describes the development and validation of a headspace GC-MS method according to ICH Q2(R1) guidelines for the detection and quantification of NDMA, NDEA, NDIPA, and NEIPA in drug products. The analytical procedure was further modified to include detection and quantitation of DMF due to the potential decomposition pathway of DMF to form dimethylamine, a known precursor for NDMA formation. The NDMA impurity was detected in the "sartan" class of drug products between 0.1 and 113 ppm. The validated analytical procedure was applied in an investigation of approaches to mitigate nitrosamine formation in metformin drug products. The developed analytical procedures provide another tool for pharmaceutical manufacturers to evaluate drug products for nitrosamine impurities.

Optimization of Microcrystalline Cellulose Production from Brewer’s Spent Grain by Acid Hydrolysis

Brewer’s spent grain (BSG) is the main insoluble solid by-product of the brewing industry. To add value to this non-wood material, microcrystalline cellulose (MCC) was prepared from BSG by alkaline pretreatment, bleaching, and subsequent acid hydrolysis to produce non-wood MCC. This study aimed to optimize MCC production using a statistical design (Box-Behnken) with three factors at three levels: acid concentration (0.5–1.5 M), hydrolysis time (70–90 min) and hydrolysis temperature (55–65 °C), to achieve the maximum yield and crystallinity of MCC derived from BSG. Results from 17 experimental runs revealed that the hydrolysis condition of 0.63 M HCl for 70 min at 61 °C yielded the highest output of 15% with a crystallinity index of 60%. The chemical structures and characteristics of MCC derived from BSG were verified by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction analysis (XRD). FT-IR analysis showed that the major wavenumbers of lignin and hemicellulose after the chemical processes (1500 cm–1 and 1735 cm–1) decreased by 21.40% and 4.60%, respectively. The XRD chromatogram revealed that the XRD characteristic peaks were sharper after the chemical treatments, indicating an increase in cellulose crystallinity due to removing lignin and hemicellulose. The crystallinity index of MCC derived from BSG ranged from 55–64%, which is comparable in quality to commercial pharmaceutical MCC, Avicel® PH-101 (67.37%). These results demonstrated that MCC from BSG was successfully prepared by acid hydrolysis under optimized conditions. BSG proved a viable non-wood source for preparing MCC for application in the pharmaceutical and nutraceutical industries.

Public attitudes toward the use of human induced pluripotent stem cells: insights from an Italian adult population

IntroductionHuman induced pluripotent stem cells (hiPSCs), derived from reprogrammed adult somatic cells, hold significant promise for disease modelling, personalized medicine, drug discovery, and regenerative therapies. Public awareness and understanding of hiPSCs are crucial for advancing research in this field. However, limited data exists on the general population’s knowledge and attitudes toward their use.MethodsThis study aimed to assess the awareness and perceptions of hiPSCs among Italian adults through a web-based survey conducted via the EUSurvey platform, using a snowball sampling approach. The survey included demographic information and mandatory questions on knowledge, awareness, and concerns regarding hiPSC technology, with responses collected on a 3-point scale. Statistical analysis was performed using chi-squared tests, with significance set at p ≤ 0.05.ResultsOut of 1874 respondents, the majority were aged 18–35 years (40.5%), female (63.4%), and university-educated (67.2%). Among those familiar with hiPSCs (54.1%, n = 1,201), 95.3% expressed willingness to donate blood samples for hiPSC generation to treat individuals with incurable diseases. Concerns about current research and therapeutic applications were low (less than 20%), but nearly half of the respondents were hesitant or opposed to the use of hiPSCs in animal experiments and their commercialization by pharmaceutical companies. Increased skepticism was observed in older, less educated, religious individuals, and those who were not blood donors. Overall, the Italian public shows strong support for hiPSC-based therapies, though reservations exist around specific ethical and economic issues.DiscussionThese findings underscore the importance of addressing public concerns through targeted educational campaigns, not only in Italy but globally, to foster a more informed and supportive environment for advancing stem cell research and its clinical applications worldwide. Similar studies have been conducted in Japan, the United States, and Sweden, but there remains a need for all countries to engage with their citizens to better understand how stem cell research is perceived locally. Such engagement is crucial for guiding international strategies in personalized medicine and regenerative therapies, ensuring that emerging technologies are met with both ethical integrity and public trust.

Patient and Physician Perspectives of Diabetic Retinopathy and Diabetic Macular Edema Diagnosis, Treatment and Progression: A Podcast Article.

Diabetic retinopathy (DR) is one of the leading causes of vision loss among people of working age. However, people with diabetes are often unaware of the importance of DR screening for preserving vision, highlighting the importance of patient education about DR and DR-related ocular and systemic comorbidities. In this podcast, three patients with different stages of DR and two ophthalmologists exchanged their views on diagnosis, treatment, and progression of DR and diabetic macular edema. The discussion revealed that DR affects not only the physical aspects of patients' lives but also their mental wellbeing. The challenges of a DR diagnosis can be compounded by communication gaps that exist between patients, physicians, and the pharmaceutical industry. Development of new therapies is currently informed mainly by physician perspectives. However, the large burden of current treatments calls for new therapeutic approaches that meet patients' needs better. The preferred method of treatment administration can differ from patient to patient and the choices between treatments that necessitate repeated visits, monitoring, and at-home care must be discussed. As such, going forward it is crucial to consider both the physician and patient perspectives in shaping the clinical landscape of DR.

Chemical Profile of Kumquat (Citrus japonica var. margarita) Essential Oil, In Vitro Digestion, and Biological Activity

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (>90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1–2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).

Mayer-Homology Learning Prediction of Protein-Ligand Binding Affinities

Artificial intelligence-assisted drug design is revolutionizing the pharmaceutical industry. Effective molecular features are crucial for accurate machine learning predictions, and advanced mathematics plays a key role in designing these features. Persistent homology theory, which equips topological invariants with persistence, provides valuable insights into molecular structures. The standard homology theory is based on a differential rule for the boundary operator that satisfies [Formula: see text] = 0. Our recent work has extended this rule by employing Mayer homology with generalized differentials that satisfy [Formula: see text] = 0 for [Formula: see text] 2, leading to the development of persistent Mayer homology (PMH) theory and richer topological information across various scales. In this study, we utilize PMH to create a novel multiscale topological vectorization for molecular representation, offering valuable tools for descriptive and predictive analyses in molecular data and machine learning prediction. Specifically, benchmark tests on established protein-ligand datasets, including PDBbind-v2007, PDBbind-v2013, and PDBbind-v2016, demonstrate the superior performance of our Mayer homology models in predicting protein-ligand binding affinities.

Role of Investing in Human Resources in Enhancing the Organizational Renewal Capabilities of the Pharmaceutical Industry

This study aims to explore the role of the dimensions investing in human resources in enhancing the organizational renewal capabilities of companies operating in the pharmaceutical industry. An online survey was conducted among a sample of (350) individuals who worked in pharmaceutical companies in the Kingdom of Saudi Arabia. The results indicate that the dimensions of investing in human resources as assessed by employees of pharmaceutical companies positively enhance all four studied dimensions of organizational renewal capabilities (strategic competence, learning orientation connectivity, leadership practices, exploiting time) for a wide range of pharmaceutical companies. The results confirm that enhancing the investing in human resources is a promising path toward improving the regulatory renewal capabilities of pharmaceutical companies. Despite the interest in investing in human resources, the lack of consensus on the specific elements of investing in human capital limits the understanding of their implications. Building on recent developments in visualizing and measuring investing in human resources, this study addresses this gap by exploring how the investing in human resources relates to the regulatory renewal capabilities of pharmaceutical companies. Received: 25 August 2024 / Accepted: 30 October 2024 / Published: 05 November 2024

USE OF PLANT GROWTH REGULATORS TO OBTAIN MINI TUBERS OF Dioscorea remotiflora Kunth IN MICROPROPAGATED PLANTS

<p><strong>Background:</strong> Camote de cerro (<em>Dioscorea remotiflora</em> Kunth) stands out as a crop option in protected agriculture in Mexico due to its agronomic benefits and its versatility in the food and pharmaceutical industries. Despite its potential, it is not commercially cultivated in the country motivating the need to develop an efficient propagation method from vegetative planting material. Previous research suggests that the use of growth retardants stimulates root growth and carbohydrates accumulation in tubers, while applying gibberellic acid (GA<sub>3</sub>) is strongly related with greater tuber production. <strong>Objective: </strong>To evaluate the effect of different growth regulators to obtain <em>D. remotiflora</em> mini tubers.<strong> Methodology: </strong>Two experiments to obtain mini tubers were carried out. The first one evaluated mediums of culture <em>in vitro</em>: MS and MS + 0.5 mg L<sup>-1</sup> paclobutrazol (PBZ). In the second, effects of foliar application of GA<sub>3</sub>, PBZ and trinexapac ethyl (TNE) were evaluated. Both experiments were carried out in two accesions of <em>D. remotiflora</em> plants propagated <em>in vitro</em> and adapted to greenhouse conditions. <strong>Results:</strong> An increase in mini tubers yield and in their weight was observed when seedlings were propagated in MS + 0.5 mg L<sup>-1</sup> PBZ and GA<sub>3</sub> was applied to foliage. <strong>Implications:</strong> The use of growth retardants showed efficiency in developing mini tubers; nevertheless, more research focusing on concentrations and combinations of these substances is needed to improve the protocol to obtain planting material. <strong>Conclusions:</strong> The observed effect of growth retardants and gibberellic acid application in <em>Dioscorea remotiflora</em> plants suggests a favorable influence in the development of mini tubers. In the long term, this phenomenon could contribute significantly to promoting viability of its commercial cultivation and rehabilitation of previously exploited areas.</p>

Impact on Human Health of Salmonella spp. and Their Lipopolysaccharides: Possible Therapeutic Role and Asymptomatic Presence Consequences

Epidemiologically, one of the most important concerns associated with introducing Salmonella spp. into the environment and food chain is the presence of asymptomatic carriers. The oncogenic and oncolytic activity of Salmonella and their lipopolysaccharides (LPSs) is important and research on this topic is needed. Even a single asymptomatic dose of the S. Enteritidis LPS (a dose that has not caused any symptoms of illness) in in vivo studies induces the dysregulation of selected cells and bioactive substances of the nervous, immune, and endocrine systems. LPSs from different species, and even LPSs derived from different serotypes of one species, can define different biological activities. The activity of low doses of LPSs derived from three different Salmonella serotypes (S. Enteritidis, S. Typhimurium, and S. Minnesota) affects the neurochemistry of neurons differently in in vitro studies. Studies on lipopolysaccharides from different Salmonella serotypes do not consider the diversity of their activity. The presence of an LPS from S. Enteritidis in the body, even in amounts that do not induce any symptoms of illness, may lead to unknown long-term consequences associated with its action on the cells and biologically active substances of the human body. These conclusions should be important for both research strategies and the pharmaceutical industry &.

MiRNAs, dd-cf-DNA, and Chemokines as Potential Noninvasive Biomarkers for the Assessment of Clinical Graft Evolution and Personalized Immunosuppression Requirement in Solid Organ Transplantation.

The use of noninvasive biomarkers may reduce the need for biopsy and guide immunosuppression adjustments during transplantation. The scientific community in solid organ transplantation currently considers that chemokines, T- and B-cell immunophenotypes, and gene expression, among other molecular biomarkers, have great potential as diagnostic and predictive biomarkers for graft evolution; however, in clinical practice, few valid early biomarkers have emerged. This review focuses on the most relevant scientific advances in this field in the last 5 years regarding the role of 3 biomarkers: miRNAs, chemokines, and ddcf-DNA, in both adult and pediatric populations. An update was provided on the scores based on the combination of these biomarkers. The most-featured articles were identified through a literature search of the PubMed database. This review provides a comprehensive analysis of the potential clinical applications of these biomarkers in the diagnosis and prediction of graft outcomes and discusses the reasons why none have been implemented in clinical practice to date. Translating these biomarkers into routine clinical practice and combining them with pharmacogenetics and pharmacokinetic monitoring is challenging; however, it is the key to present/future individualized immunosuppressive therapies. It is essential that they be shown to be applicable and robust in real-life patient conditions and properly evaluate their added value when combined with the standard-of-care factor monitoring for graft clinical assessment. Partnership strategies among scientists, academic institutions, consortia, including expert working groups and scientific societies, and pharmaceutical and/or biotechnology companies should promote the development of prospective, randomized, multicenter intervention studies for adequate clinical validation of these biomarkers and their monitoring frequency, and their commercialization to make them available to transplant physicians.

Valorization of Fish Processing by-Products: Biological and Functional Properties of Bioactive Peptides

Abstract Purpose of Review This review explores the potential of fish by-products as a source of bioactive peptides for the food, pharmaceutical, and cosmetic industries. Focusing on their diverse bioactive and functional properties, it offers insights into their industrial utilization, contributing to a better understanding of their applications. Recent Findings Fish processing by-products, including wastewater and solid residues, serve as valuable sources of bioactive peptides exhibiting a remarkable range of biological activities, such as antioxidant, antimicrobial, and antihypertensive properties. These peptides exhibit a wide range of functional properties, such as solubility, water holding, fat binding, foaming, and emulsifying capacities. Moreover, they show significant potential for various industrial applications. Summary Bioactive peptides derived from fish by-products are attracting interest in multiple industries due to their diverse biological activities and functional properties. These peptides have emerged as a valuable and largely untapped resource, as they can be extracted from underutilized, or waste materials generated during fish processing operations. Graphical Abstract

Comparative assessment of a COVID-19 vaccine after technology transfer to Iran from critical quality attributes to clinical and immunogenicity aspects

During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer.

The role of Pharmaceutical Marketing in Prescribing Decisions in a Developing Country: A Comprehensive Study Exploiting Theory of Planned Behaviour

Background: Prescription medicines have become a major component of health systems in both developed and developing countries contributing to, may be, more than half of the total health care expenditure in the developing countries. Although literature directly attributing rise in medicines expenditure to prescribers’ decision, but still only a few researches had employed studies with sound theoretical foundations to comprehensively examine prescribing decision behaviours. Our objective was to investigate potentially modifiable factors, which may influence prescribing decisions of physicians employing theory of planned behaviour. Method: A quantitative survey approach was used to investigate the proposed hypotheses. Population was physicians in outpatient clinics in both private and governmental hospitals in Sana’a, capital city of Yemen. A structured questionnaire was designed to measure the influence of drug-promoting marketing techniques on physicians’ prescribing decisions. Data was collected through an anonymous survey questionnaire. The hypotheses were tested by multiple regressions analysis. Ethical approval was obtained from the Ethical Committee of the Ministry of Public Health and Population (MoPHP), and participants provided written consent before enrolling in the study. Result: Physicians admitted the presence of promotional influence on their prescribing decision. The study revealed that receiving low-value promotional items, belief of physicians that it is appropriate to accept both low- and high-value promotional items, physicians’ exposure to company-direct sources of information, and drug promotion-related factor all are positively and significantly related to physicians’ prescribing decisions (? = 0.438, p <0.001; ? = 0.089, p =0.027; ? = 0.157, p <0.001; ? = 0.093, p =0.032; and ?= 0.118, p = 0.007 respectively). Conclusion: This research clarified the role played by pharmaceutical companies to influence prescribing decisions of physicians. Therefore, could provide theoretical framework for policymakers in Yemen, and other countries with similar conditions, to develop a suitable policy and strategy in terms of drug promotion.

Vetiver [Chrysopogon zizanioides (L.) Roberty]: An Aromatic Root Crop for Soil and Water Conservation

Khus grass or vetiver (Chrysopogon zizanioides (L.) Roberty) is a hardy perennial aromatic grass with long enormous tufted fibrous root system. Commercially, dry roots are used for extraction of essential oil that acts as a fixative in perfumery industry worldwide. Besides, vetiver roots are used in medicinal and pharmaceutical industries to treat rheumatism, arthritis, gouty joints, paralysis and indigestion. Roots and root oil have strong anti-oxidant, stimulant, carminative and cooling properties and used in Ayurvedic medicines. Traditionally, vetiver plants are being used to cultivate across hill slopes, waterways and wastelands to reduce runoff and soil conservation. During 1990’s World bank was promoting use of vetiver grass as contour vegetative barrier in upland farming systems of Asian and African countries. Further, recent studies report the use of vetiver in phytoremediation, reclamation of mined lands and soil and water detoxification in addition to carbon sequestration. Due to introduction of modern cultivation practices, traditional soil conservation practices are being vanished gradually over a period of time. In this regard, an attempt has been made to review the scientific evidence for use of vetiver grass as a soil and water conservation measure along with phytoremediation.

Scope of Ayurvedic Nasal Instillation Therapy (Nasya Karma) in Cosmetology: A Review

Cosmetics has become an important & influential part of human’s daily life in today’s world due to one’s tendency for self-care & regard as it boost their confidence and self-esteem. The increase in daily use of these various cosmetics has also garnered a lot of increased demand in pharmaceutical industry; resulting into various harmful & chemical drug practices for monetary gain also leading to lots of side effects of such cosmetics on human skin. The beauty ailments that commonly affect people are hair fall, greying of hairs, dandruff, acne, melasma, minor skin and oral disorders. These problems are not only difficult to treat but also requires a lot of expenses too. Ayurveda has mentioned various methods to tackle these problems as Ayurvedic scholars has put heavy weightage on importance of beauty; external as well as internal in both male and female and has described treatments for these ailments in ancient texts such as Nasya Karma [Ayurvedic Nasal Instillation Therapy]. Nasya is one of famous Panchakarma procedure used for management of above mention cosmetic ailments. It is a procedure in which herbal drug [oil/decoction/extract/powder] is instilled through nasal route and is highly appreciated for its therapeutic value in diseases related to Urdhava-Jatrugata [above clavicle region]. In this article, we have discussed various types and probable action of Nasya Karma [Ayurvedic Nasal Instillation Therapy] in these disorders and how this single Ayurvedic procedure can be a one stop solution for multiple beauty ailment and can be helpful in reaching the goal of enhancement of beauty with assurance of safety and prevention from any harmful effect.

Integration of CRISPR/Cas9 with multi-omics technologies to engineer secondary metabolite productions in medicinal plant: Challenges and Prospects.

Plants acts asliving chemical factories that may create a large variety of secondary metabolites, most of which are used in pharmaceutical products. The production of these secondary metabolites is often much lower. Moreover, the primary constraint after discovering potential metabolites is the capacity to manufacture sufficiently for use in industrial and therapeutic contexts. The development of omics technology has brought revolutionary discoveries in various scientific fields, including transcriptomics, metabolomics, and genome sequencing. The metabolic pathways leading to the utilization of new secondary metabolites in the pharmaceutical industry can be identified with the use of these technologies. Genome editing (GEd) is a versatile technology primarily used for site-directed DNA insertions, deletions, replacements, base editing, and activation/repression at the targeted locus. Utilizing GEd techniques such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9), metabolic pathways engineered to synthesize bioactive metabolites optimally. This article will briefly discuss omics and CRISPR/Cas9-based methods to improve secondary metabolite production in medicinal plants.

Improvement of succinate production from methane by combining rational engineering and laboratory evolution in Methylomonas sp. DH-1

Recently, methane has been considered a next-generation carbon feedstock due to its abundance and it is main component of shale gas and biogas. Methylomonas sp. DH-1 has been evaluated as a promising industrial bio-catalyst candidate. Succinate is considered one of the top building block chemicals in the agricultural, food, and pharmaceutical industries. In this study, succinate production by Methylomonas sp. DH-1 was improved by combining adaptive laboratory evolution (ALE) technology with genetic engineering in the chromosome of Methylomonas sp. DH-1, such as deletion of bypass pathway genes (succinate dehydrogenase and succinate semialdehyde dehydrogenase) or overexpression of genes related with succinate production (citrate synthase, pyruvate carboxylase and phosphoenolpyruvate carboxylase). Through ALE, the maximum consumption rate of substrate gases (methane and oxygen) and the duration maintaining high substrate gas consumption rates was enhanced compared to those of the parental strain. Based on the improved methane consumption, cell growth (OD600) increased more than twice, and the succinate titer increased by ~ 48% from 218 to 323 mg/L. To prevent unwanted succinate consumption, the succinate semialdehyde dehydrogenase gene was deleted from the genome. The first enzyme of TCA cycle (citrate synthase) was overexpressed. Pyruvate carboxylase and phosphoenolpyruvate carboxylase, which produce oxaloacetate, a substrate for citrate synthase, were also overproduced by a newly identified strong promoter. The new strong promoter was screened from RNA sequencing data. When these modifications were combined in one strain, the maximum titer (702 mg/L) was successfully improved by more than three times. This study demonstrates that successful enhancement of succinic acid production can be achieved in methanotrophs through additional genetic engineering following adaptive laboratory evolution.

A new insight into the mechanism of loading of Granisetron, Naltrexone and Risperidone in poly(ortho ester) and poly (lactic-co-glycolic acid) as the controlled release drug delivery systems using a computational molecular approach

Owing to the good biocompatibility, bioavailability, biodegradability, and low toxicity of polymeric nanoparticles, considerable research interest has been generated. These polymeric carriers enhance the therapeutic index and improve controlled drug release. In this study, molecular dynamics (MD) simulation of six designed systems were conducted to compare poly(ortho ester) (POE) and poly (lactic-co-glycolic acid) (PLGA) polymeric nanoparticles as carriers and delivery systems for three drugs: Granisetron, Naltrexone, and Risperidone. These drugs are FDA-approved under the brand name SUSTOL (Granisetron for anti-nausea and vomiting post-heavy chemotherapy), VIVITROL (Naltrexone for managing alcohol or opioid use disorder), and RISPERDAL CONSTA (Risperidone for treating schizophrenia). Various parameters, such as interaction energy, radius of gyration (Rg), solvent accessible surface area (SASA), distance, hydrogen bond, radial distribution function (RDF), and root mean square fluctuation (RMSF), were investigated. The MD simulations show good consistency with FDA-approved data, clearly illustrate why PLGA is suitable for NAL and RIS, and POE for GRS, as carriers in drug delivery. The findings, detailing mechanisms of polymer-drug interactions, have potential applications in (i) manufacturing and production of novel sustained-release drugs and biopolymers, (ii) identifying suitable patterns, and (iii) rationally designing new controlled-release drugs based on future artificial intelligence methods.

The Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.

Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification (metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST) guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the "Translatability of MetID In Vitro Systems Working Group" was created within the Translational and ADME Sciences Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices have been at predicting circulating human metabolites.The results of this survey are presented as an initial snapshot of current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater translational capability are also provided.