Drug Safety Research Articles

A Systematic Patent Review (2008-2023) for Treatment in Pregnancy.

During pregnancy, the woman's body undergoes anatomical and physiological changes, making this period susceptible to maternal-fetal diseases and complications. The consequences of not treating pregnant women include premature birth, low birth weight fetuses, and postnatal behavior disorders. Developing new therapies can accelerate the discovery of safe and effective drugs, contributing to designing novel natural and synthetic products to treat complications the pregnancy. This study aimed to carry out a patent review to identify and explore trends in innovation and therapeutic strategies for treating pregnant women. The Espacenet and WIPO databases were used, with the inclusion criteria being the keywords "pregnancy and drug" and code A61k, from 2008 to 2023, and as exclusion were the access to the patent and focus on human pregnant women. After the final screening, 32 patents were selected, with strategies for the treatment of diseases in pregnant women. Of these, 20 patents are on preclinical studies on animals and 12 on pregnant women. It was observed that universities lead the ranking of applications (17/32), and China has the highest number of patents (18/32). Most findings contain herbal medicines and/or the association of natural extracts with synthetic drugs. From this perspective, new drug administration systems were also developed, which can be a promising source for obtaining new medicines for the treatment of pregnant women; however, research is still limited and shows a gap in stimulating the rapid development of safe drugs that improve the health of pregnant women.

Investigating the Safety Profile of Fast-Track COVID-19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study.

The US Food and Drug Administration (US FDA) granted emergency use authorization (EUA) for multiple coronavirus disease 2019 (COVID-19) drugs as a medical countermeasure during the COVID-19 pandemic. Despite these drugs' fast-track nature, concerns persist regarding their efficacy and potential adverse effects. Thus, the continuous surveillance and understanding of these drugs' safety profiles are crucial in such scenarios. Using the FDA Adverse Event Reporting System (FAERS) database, we aimed to compare the adverse drug reactions (ADRs) of four fast-track COVID-19 drugs to explore the potential of real-world data for providing prompt feedback in clinical settings. To evaluate the post-marketing safety of fast-track COVID-19 drugs, we descriptively evaluated the ADRs of four COVID-19 drugs (bebtelovimab, molnupiravir, nirmatrelvir/ritonavir, and remdesivir) using FAERS data reported from January 2020 to June 2022. We examined FAERS case records of COVID-19 drugs reported as the "primary suspect drug" as a case group and the records of other drugs as the control. "Serious adverse drug reactions (SADRs)" were defined based on FDA guidelines. Using reporting odds ratios, disproportionality analysis was conducted to determine significant signals for ADRs related to each of the four drugs compared with those of others, both at the preferred term (PT) and system organ class (SOC) levels. To explore the occurrence of reporting each serious outcome reported to the four drugs, we fitted logistic regression models, adjusting for age and sex. During the study period, 5 248 221 cases were submitted to FAERS, including 17 275 cases of the four COVID-19 drugs: bebtelovimab (532 cases), molnupiravir (1106 cases), nirmatrelvir/ritonavir (9217 cases), and remdesivir (6420 cases). A total of 64, 46, 116, and 207 PTs with significant disproportionality were identified for each drug, respectively. "Infusion-related reaction" (18.4%), "diarrhea" (7.4%), "dysgeusia" (11.4%), and "increased alanine aminotransferase" (14.5%) were the most frequently reported SADRs for bebtelovimab, molnupiravir, nirmatrelvir/ritonavir, and remdesivir, respectively. Among the 27 SOCs, statistically significant signals were observed in 10, 3, 0, and 8 SOCs for bebtelovimab, molnupiravir, nirmatrelvir/ritonavir, and remdesivir, respectively. Remdesivir showed a higher occurrence for the reporting of death or life-threatening ADRs compared with the control (adjusted odds ratio (OR) = 2.44, 95% confidence interval (CI) = 2.23-2.59; adjusted OR = 1.82, 95% CI = 1.64-2.02, respectively). We identified potential ADRs associated with COVID-19 drugs and provided insights into their real-world safety. This study demonstrated that real-world data and real-time safety reviews could be effective methods for the timely detection of ADR signals of drugs that have received fast-track approval, as exemplified by COVID-19 drugs. These findings underscore the importance of the continued surveillance, efficient data processing, and establishment of automated pipelines for real-time safety reviews.

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Glutathione inhibits lung cancer development by reducing interleukin-6 expression and reversing the Warburg effect

Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticancer effect of GSH in patients with pulmonary nodules. Thirty patients with pulmonary nodules were treated with GSH intravenously for 10 days at a dose of 1.8 g/d, followed by oral administration of the drug at a dose of 0.4 g three times daily for 6 months. The results showed that GSH treatment promoted nodule absorption and reduced the IL-6 level in the peripheral blood of the patients. GSH reduced IL-6 expression in inflammatory BEAS-2B and lung cancer cells and inhibited the proliferation of lung cancer cell lines in vitro. In addition, GSH reduced IL-6 expression by decreasing ROS via down-regulating PI3K/AKT/FoxO pathways. Finally, GSH reversed the Warburg effect, restored mitochondrial function, and reduced the IL-6 expression via PI3K/AKT/FoxO pathways. The in vivo experiment confirmed that GSH inhibited lung cancer growth, improved mitochondrial function, and reduced the IL-6 expression by regulating key enzymes via the PI3K/AKT/FoxO pathway. In conclusion, we uncovered that GSH exerts an unprecedentedly potent anti-cancer effect to prevent the transformation of lung nodules to lung cancer by improving the mitochondrial function and suppressing inflammation via PI3K/AKT/FoxO pathway. This investigation innovatively positions GSH as a potentially safe and efficacious old drug with new uses, inhibiting inflammation and early lung cancer. The use of the drug offers a promising preventive strategy when administered during the early stages of lung cancer.

Histidine-derived carbon dots for redox modulation and gut microbiota regulation in inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a chronic inflammation of the colon that is becoming increasingly prevalent. As a result, there is a growing demand for safe, effective, and non-addictive drugs. Herein, we are inspired by using carbon dots-based nanomedicines to regulate redox balance and alleviate inflammatory diseases. Specifically, histidine-derived carbon dots (His-CDs) with antioxidant and multi-enzyme (superoxide dismutase, catalase) activities are synthesized, which not only improve intestinal redox balance, but also demonstrate promising potential in modulating gut microbiota for the treatment of IBD. To understand that underlying activities mechanisms of His-CDs, their precursors, structures, and band gaps are carefully analyzed. Our investigations show that His-CDs effectively reduce oxidative damage to cells and nematodes by scavenging free radicals. Furthermore, we confirm the anti-IBD effects of His-CDs at both cellular and mouse levels. Importantly, our research reveal that His-CDs restore intestinal homeostasis in colitis by regulating the gut microbiota. We further validate this finding through fecal microbiota transplantation, which demonstrate an increase in the abundance of beneficial bacteria in the intestinal tract following the administration of His-CDs. This investigation not only expands the knowledge of nanozymes, but also offers a promising nanomedicine approach for IBD therapy.

Drug Repurposing against Novel Therapeutic Targets in Plasmodium falciparum for Malaria: The Computational Perspective.

Malaria remains one of the most challenging tropical diseases. Since malaria cases are reportedly alarming in terms of infections and mortality, urgent attention is needed for addressing the issues of drug resistance in falciparum malaria. High throughput screening methods have paved way for rapid identification of anti-malarial. Furthermore, drug repurposing helps in shortening the time required for drug safety approvals. Hence, discovery of new antimalarials by drug repurposing is a promising approach for combating the disease. This article summarizes the recent computational approaches used for identifying novel antimalarials by using drug target interaction tools followed by pharmacokinetic studies.

A narrative review of veterinary pharmacovigilance situations and prospects in East African countries

BackgroundVeterinary pharmaceuticals must be safe and effective for treating and preventing diseases in animal sectors. Strict adherence to regulations at every stage of production, storage, and administration is necessary as the global sector grows in order to lower the possibility of adverse veterinary drug events. Strong pharmacovigilance regulatory systems are critical in monitoring and managing safety concerns related with veterinary pharmaceuticals.ObjectiveThis review aimed to investigate the implementation of veterinary pharmacovigilance, collaborative initiatives, and reporting practices within the veterinary sector across East African countries.MethodsA thorough search was performed using online platforms such as Google Scholar, PubMed, the Web of Sciences, and regulatory Web sites. The search strategies relied heavily on selecting relevant published findings related to veterinary pharmacovigilance status, veterinary adverse drug event reporting practice, and collaborative efforts in veterinary pharmaceutical sectors within the East African landscape. This article search approach confirmed the inclusion state of veterinary pharmacovigilance and associated collaborative initiatives in the region.ResultsIn comparison to more developed regions, the review indicated that the veterinary pharmacovigilance system in East African countries was still in its early state. A strong legislative foundation and a large commitment from the veterinary profession are needed to establish a nationwide veterinary pharmacovigilance system. The review reveals a significant lack of consistency in the infrastructure of veterinary pharmacovigilance among the countries of East Africa. Tanzania, Kenya, and Ethiopia have some institutional processes for veterinary pharmaceutical safety, but they lack thorough documentation, which suggests that this systems still require improvement. The analysis emphasizes how inadequate the reporting systems are for adverse veterinary medication events in the majority of East African nations. Given the challenges East Africa faces, customized strategies are required to guarantee the safety and oversight of veterinary medications and improve veterinary pharmacovigilance. For systems to be more effective, veterinary pharmaceutical legal frameworks must be strengthened and stakeholder collaboration must be improved. Stakeholders include legislators, law enforcement, customs officials, regulatory organizations, scientists, pharmaceutical businesses, veterinarians, farmers, and the general public.ConclusionA multidisciplinary strategy is needed to solve current gaps in veterinary pharmacovigilance and improve overall veterinary drug safety in East Africa. It is feasible to create more reliable methods for tracking and guaranteeing the safety of veterinary medications by combining the efforts of numerous stakeholders, including as legislators, regulatory agencies, veterinary practitioners, and the general public.

A Holistic Harm Reduction Center Model: A Commentary

Substance addiction is a chronic, relapsing disorder characterized by compulsive drug seeking, loss of control over consumption, and a negative emotional state when access to the drug is restricted. Substance Use Disorders (SUDs) are associated with severe health issues including suicide and co-occurring diseases like HIV and hepatitis C, and mental health problems. Although the present SUD treatment models prioritize abstinence, achieving abstinence during a treatment episode is challenging as majority of individuals with SUDs continue using drugs during treatment. To address this challenge in the current SUD treatment model, harm reduction has emerged as a strategy that focuses on interventions such as naloxone distribution, syringe services, safe drug use education and other strategies that reduce harmful outcomes such as substance-related overdose death and disease transmission while improving quality of life. This commentary proposes a Holistic Harm Reduction Model that can be incorporated by harm reduction centers aimed at reducing risky drug use behavior and overdose deaths, and ultimately improving public health outcomes in the community. The proposed holistic model includes new components such as trauma-informed care and referral and a brief mindfulness intervention along with the already existing harm reduction approaches such as Licensed Practical Nurses (LPNs) and harm reduction managers to provide comprehensive healthcare services, distribution of supplies; education; referral and linkage to other services, including medications for substance use disorder; and participant data collection and analysis.

Correction of iron deficiency and iron deficiency anemia in women of reproductive age: choice of a drug within framework of concept of patient blood management

The article presents a review of the literature and our own data on the problem of prevention, diagnosis and treatment of iron deficiency and iron deficiency anemia in patients of reproductive age with a burdened somatic status with the development of a chronic inflammatory process. In the concept of patient blood management (PBM), the diagnosis and treatment of anemia in patients with gynecological diseases requiring subsequent surgical treatment is given paramount importance, since anemia and iron deficiency are considered risk factors for worse treatment outcomes for patients. Women with gynecological pathology often have diseases that are accompanied by the development of a systemic inflammatory response, which leads to activation of hepcidin protein synthesis and the development of so-called anemia of inflammatory diseases. Data are presented indicating the effectiveness and safety of the sucrosomial iron drug (SiderAL® Forte) in obstetric and gynecological patients with increased levels of C-reactive protein in combination with iron deficiency and iron deficiency anemia. The increase in ferrokinetic parameters in patients receiving sucrosomial iron is due to the unique physicochemical and pharmacokinetic characteristics of sucrosome, which provides protection of sucrosomial iron from the effects of gastric juice, excluding contact with the mucous membrane of the gastrointestinal tract and its absorption through special M-cells of the small intestinal mucosa followed by the release of iron in liver cells. Sucrosomial iron is novel, convenient, effective, and well tolerated compared with traditional oral iron supplements.

Correlation Analysis Among the Chemical Composition and Cytotoxic and Antioxidative Activities of a Tessaria absinthioides Decoction for Endorsing Its Potential Application in Oncology.

Historically, botanical preparations have been used to improve human health. Their active ingredients are influenced by multiple factors such as intraspecies variations, environmental conditions, collection time and methods, and the part of the plant used. To ensure the efficiency and safety of these herbal drugs, qualitative and quantitative analyses are required. A Tessaria absinthioides decoction (DETa) was reported as having hypocholesterolemic, anti-inflammatory, cytotoxic, antitumor, and antioxidative properties. This work aimed to analyze DETa by correlating its chemical composition with cytotoxic and antioxidative properties, with the aim of promoting research on it as an anticancer agent. DETa collections (2017, 2018, 2019, and 2022) were analyzed by UHPLC-DAD, UHPLC-DAD-FLD, and UPLC-MS/MS; cytotoxicity was assessed on the MCF-7 breast cancer cell line; antioxidative capacity was evaluated by the DPPH and FRAP methods; and correlation analysis was used to determine biological and chemical markers. The results provide evidence that biological activities were consistent across the collections. Among the quantified compounds, apigenin, naringin, gallocatechin gallate, ginnalin A, myricetin, epicatechin, OH-tyrosol, quercetin, and chlorogenic, tessaric, p-coumaric, vanillic, caffeic, caftaric, ellagic, and rosmarinic acids correlated as bioactive and chemical markers. Moreover, tessaric acid could be established as a species marker. Altogether, these findings add relevant information to DETa properties, encouraging further exploration of its potential application as an anticancer botanical.

A Study on the Change of Hair Conditions Before and After Using Aroma Shampoo Bar

In this study, changes in hair condition after using aroma shampoo bars were investigated. Aroma shampoo was produced in the form of a bar (100 g) by complying with cosmetic safety standards in accordance with the Ministry of Food and Drug Safety notice. The essential oils used in aroma shampoo bars were lavender, juniper berries, cypress, peppermint, cedarwood, ylang ylang and rosemary as reference to previous studies. The subjects of this study were adults in their 20s or older, and consisted of two groups: a control group, 23 people and the experimental group, and 23 people. Aroma-free shampoo bars were used as the control group, and an aroma-containing shampoo bar was used as the experimental group. Measurement was measured once a week for 4 weeks before and after use. The hair measurement site is the top of the head, occipital region, left and right sides of the forehead. Measurement was performed with Aram Hubis’ ASG (AI-Scalp Grader). As a result of the study, there was a significant increase in hair condition changes in the density and number of the left forehead and occipital regions in the experimental group using aroma shampoos. This study has academic and social significance in that cleaning products, not products that nourish hair, can positively change hair condition and that it proved the effect of essential oils with quantitative data.

The Effects of Systemic Tranexamic Acid Administration on Drainage Volume, Duration of Drain Placement, and Length of Hospital Stay in Skin- and Nipple-Sparing Mastectomies with Immediate Expander-Based Breast Reconstruction.

Background: Skin- (SSM) and nipple-sparing (NSM) mastectomies are frequently performed surgeries with a considerable risk for post-operative hematoma or seroma. Tranexamic acid (TXA) is a potent antifibrinolytic drug commonly used in many surgical fields but rather novel in plastic and, specifically, breast surgery. This study investigates the influence of TXA in patients undergoing SSM or NSM with expander-based reconstruction (EbR) on post-operative outcomes. Methodology: A retrospective study was conducted on 132 patients undergoing uni- or bilateral SSM or NSM with EbR between May 2015 and March 2022. Patients receiving systemic TXA treatment for 48 h following a standardized protocol were compared to those who received no treatment. Multivariable linear regression was performed to identify influencing factors and quantify their effect on drainage volume, duration of drain placement, length of hospital stay, post-operative bleeding, and seroma formation. Results: The 132 patients underwent a total of 155 mastectomies (72 in the TXA group, 83 in the control group). TXA significantly reduced drainage volume (-22.3 mL, p = 0.011). Duration of drain placement and length of hospital stay were significantly shorter in the TXA group (p < 0.001 and p = 0.001). No significant side effects were reported. Conclusion: TXA is a safe drug if administered respecting the well-defined contraindications. Systemic TXA administration significantly reduces drainage volume in patients undergoing SSM or NSM and should encourage surgeons to reconsider using drains in post-operative protocols. Duration of drain placement and length of hospital stay were significantly reduced in the TXA group but other factors like resection weight might have a more substantial impact.

Stability Indicating High‐performance Liquid Chromatography Method for Quantification of Amoxapine and Characterization of Forced Degradation Products Employing Quadrupole‐Time of Flight Mass Spectrometry

ABSTRACTAmoxapine, a tricyclic antidepressant, has been widely used for long‐term treatment of depression along with other psychiatric disorders involving neurosis, agitation, and anxiety. The drug may undergo degradation during manufacturing, transportation, and storage. To ensure drug safety, both identification and characterization of the degradation products (DPs) should be considered. Accordingly, a sensitive and selective stability‐indicating assay method was developed for amoxapine using high‐performance liquid chromatography (HPLC). The amoxapine drug was subjected to acidic hydrolysis, basic hydrolysis, and oxidation separately. The degradation susceptibility of the amoxapine was found to be in the order of Acid hydrolysis &gt; Oxidation &gt; Base hydrolysis. The developed method was validated as per the International Council for Harmonization Q2(R2) guideline. Further, LC‐electrospray ionization‐quadrupole‐time of flight‐tandem mass spectrometry was employed for the identification and characterization of the DPs formed under stress conditions. The study revealed that under accelerated stress conditions, three hydrolytic DPs and one oxidative DP were formed. Three of the four DPs were found to be novel and never reported before. In addition, a plausible mechanism representing the formation of all DPs has also been established.

Prevalence and influence factor of drug-related problems in inpatients with kidney disease: a prospective single central study.

To investigate the prevalence and influencing factors of drug-related problems (DRPs) in inpatients with kidney disease to provide reference data for pharmaceutical care. The basic information, diagnoses, and medication reconciliation (MR) of inpatients in the Department of Nephrology at our hospital between October 2020 and September 2021 were collected. The Chinese-modified DRP version based on the PCNE classification (Version 9.1) was used to assess, intervene and statistically analyze the results of the patients' DRPs. The influence factor of DRPs in inpatients with kidney disease was analyzed by the multivariate binary logistic regression. Of 623 patients included in this study, 132 (21.80%) had DRPs. The prevalence of anemia was significantly higher in patients with DRPs than those without DRPs (43.18% vs. 28.72%, p < 0.05), the mean number of drug types consumed (7.25 ± 3.44 with DRPs vs. 5.93 ± 3.58 without DRPs, p < 0.05) and the proportion of ≥5 drugs (%) (79.55% with DRPs vs 58.04% without DRPs, p < 0.05) were significantly increased. In addition, the prevalence of hypertension (76.52% vs. 68.64%), diabetes (27.27% vs. 22.20%) and hyperuricemia (16.67% vs. 13.65%) in DRP patients were higher than those without DRPs, but there was no statistical difference (p > 0.05). The logistic regression analysis showed that patients with anemia (OR = 1.702, 95%CI: 1.146-2.529, p = 0.008), average number of medication types taken (OR = 1.089, 95%CI: 1.034-1.147, p = 0.001) significantly increased the risk of DRPs. The distribution of harm levels was as follows: 78 problems (59.09%) were level C, 29 (21.97%) were level B, 10 (7.58%) were level D, 7 (5.30%) were level A, 7 (5.30%) were level E, and 1 (0.76%) were level F. All DRPs were resolved after 128 interventions. Renal anemia, the average number of drug varieties consumed, and the proportion of ≥5 drugs are associated with the occurrence of DRPs. Pharmacists conducting MR services can reduce DRPs of inpatients in the department of nephrology and ensure patient drug safety.

Harnessing bacterial metabolites for enhanced cancer chemotherapy: unveiling unique therapeutic potentials.

Cancer poses a serious threat to health globally, with millions diagnosed every year. According to Global Cancer Statistics 2024, about 20 million new cases were reported in 2022, and 9.7 million people worldwide died of this condition. Advanced therapies include combination of one or more treatment procedures, depending on the type, stage, and particular genetic constitution of the cancer, which may include surgery, radiotherapy, chemotherapy, immunotherapy, hormone therapy, targeted therapy, and stem cell transplant. Also, awareness about lifestyle changes, preventive measures and screening at early stages has reduced the incidence of the disease; still, there is a major failure in controlling the incidence of cancer because of its complex and multifaceted nature. With increasing interest in bacterial metabolites as possible novel and effective treatment options in cancer therapy, their main benefits include not only direct anticancer effects but also the modulation of the immune system and potential for targeted and combination therapies. They can therefore be used in combination with chemotherapy, radiotherapy, or immunotherapy to improve outcomes or reduce side effects. Furthermore, nanoparticle-based delivery systems have the potential to enhance the potency and safety of anticancer drugs by providing improved stability, targeted release, and controlled delivery.

Three-Dimensional Printing Technology in Drug Design and Development: Feasibility, Challenges, and Potential Applications

Background/Objectives: The present investigation evaluates the impact of 3D-printing technology on the design of pharmaceutical drugs, considering the feasibility issues and problems concerning technological, pharmaceutical, and clinical matters. This paper aims to review how 3D printing can modify the traditional manufacturing of drugs with personalized medicine-therapy outcomes being individualized and optimized, hence improving patients’ compliance. Methods: The historical development of 3D printing from rapid prototyping to advanced pharmaceutical applications is discussed. A comparison is then made between traditional drug manufacturing approaches and the different techniques of 3D printing, including stereolithography, material extrusion, and binder jetting. Feasibility is assessed based on clinical trials and studies evaluating the efficacy, safety, bioavailability, and cost-effectiveness of 3D-printed drugs. Results: Current evidence indicates that material selection, regulatory barriers, and scalability issues are some of the major challenges to be overcome for wider acceptance. Other matters, such as ethical issues concerning patient data privacy, the misuse of 3D-printing technology, and technical complexities related to pharmaceutical 3D printing, are discussed further. Future applications also include bioprinting and in situ printing together with their implications for personalized drug delivery, which will also be discussed. Conclusions: This review stresses that intersectoral collaboration and the updating of regulatory frameworks are a must to overcome the barriers that confront 3D-printing applications in drug development. can could be an opportunity for innovative licensing and manufacturing techniques in pharmaceutical product development that can change the paradigm of personalized medicine through modern printing techniques.

Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice.

To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.

Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication

Abstract Bispecific apoptosis triggers (BATs) are innovative bispecific antibodies designed to simultaneously target both a tumor-associated antigen and a cancer cell’s death receptor, thereby directly activating the extrinsic apoptotic pathway to induce death of cancer cells. This unique mechanism distinguishes BATs from antibody-drug conjugates (ADCs), which rely on cytotoxic drugs, and bispecific immune cell engagers such as bispecific T-cell engagers (BiTEs) and bispecific natural killer cell engagers (NKCEs), which recruit immune cells to eliminate target cancer cells. BATs offer significant potential advantages in clinical efficacy and safety over ADCs and BiTEs. Although the field is still emerging, recent advancements are highly promising, and analysis of preclinical and clinical data of DR5-targeting antibodies have been pivotal in outlining the criteria for the next generation of effective and safe medicines. Antibodies found inactive in preclinical testing were also found to be clinically ineffective, whereas antibodies with minimal preclinical results demonstrated moderate clinical activity. All clinical DR5-targeting antibodies were well tolerated by patients even at high doses (with the exception of TAS266 due to its unique design). These findings underscore the predictive value of robust preclinical models on clinical outcomes. Notably, first-in-class BAT, Cancerlysin™ IMV-M, demonstrated potent efficacy in diverse xenograft cancer models and safety in non-human primates, marking a significant advancement in developing safe and effective anti-cancer drugs.

Modelling hemodynamics regulation in rats and dogs to facilitate drugs safety risk assessment.

Pharmaceutical companies routinely screen compounds for hemodynamics related safety risk. In vitro secondary pharmacology is initially used to prioritize compounds while in vivo studies are later used to quantify and translate risk to humans. This strategy has shown limitations but could be improved via the incorporation of molecular findings in the animal-based toxicological risk assessment. The aim of this study is to develop a mathematical model for rat and dog species that can integrate secondary pharmacology modulation and therefore facilitate the overall pre-clinical safety translation assessment. Following an extensive literature review, we built two separate models recapitulating known regulation processes in dogs and rats. We describe the resulting models and show that they can reproduce a variety of interventions in both species. We also show that the models can incorporate the mechanisms of action of a pre-defined list of 50 pharmacological mechanisms whose modulation predict results consistent with known pharmacology. In conclusion, a mechanistic model of hemodynamics regulations in rat and dog species has been developed to support mechanism-based safety translation in drug discovery and development.

Development of a Medical Device Lifecycle Research Database at the MFDS

Abstract So-called big data are potentially useful in the healthcare field and are of interest to researchers, industry, and government agencies. Over the past 10 years, Europe, the United States, and Asia have been making efforts to collect and systematically manage information on the entire process from clinical trials to follow-up management of medical devices (MD). We developed MD lifecycle research database at the Ministry of Food and Drug Safety (MFDS) of the Republic of Korea, consisting of 61 tables and 2,053 variables. The MFDS possesses statistical information on all MD, pharmaceuticals, foods, and human tissues produced and distributed. The information in the database is categorized according to four MD lifecycle phases-clinical trial, approval, production, and post-approval. For the clinical trial phase, the database contains information on planning and approval of clinical trial and non-clinical trial. The approval phase includes information on models, raw materials, quality, and changes, while the production phase stores information on production, import, export, supply and use. For the last step, follow-up management phase, provide information on post-marketing safety management, risk management, and administrative disposition. All four steps are linked based on primary key, so it is possible to understand information on the overall MD lifecycle. The MD Lifecycle Research Database will help strengthen the industry’s competitiveness in terms of cost-effectiveness in MD development and facilitate policy monitoring by improving its utilization in the public interest. This database contains information on all MD produced and distributed in Korea depending on the phases of the MD lifecycle, and data is easily accessible due to the lack risk of personal information exposure, so it can be widely used by individual researchers, industries, academia, and governments. Funding This research was supported by a grant (22063MFDS498) from ministry of food and drug safety in 2024. Key messages • We developed a medical device lifecycle database that enables tracking management according to the medical device lifecycle. • This database can be used as a scientific basis to ensure the safety, effectiveness, and efficiency of medical devices.