Oncology's trial and error: Analysis of the FDA withdrawn accelerated approvals.

Launched in 1992, the FDA accelerated approval program grants drugs indicated in rare/life threatening diseases the ability to be marketed at a faster pace than through the traditional track. Each manufacturing company presents its drug to the FDA, and within 60 days it will determine if the drug is eligible for this path. Many drugs that were initially approved through this route, subsequently did not demonstrate their clinical benefits. With cancer being a leading cause of death, a vast majority of drugs that have been approved/withdrawn from this pathway are indicated within oncology. There are a wide variety of cancer subtypes and therapeutic target sites that these drugs have been evaluated for. Herein, is an overview of the 17 oncology drugs, spanning 22 cancer-related indications, that had been approved within the accelerated route and subsequently withdrawn.

Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

Detection technologies of volatile organic compounds in the breath for cancer diagnoses.

Although there are new approaches in both cancer treatment and diagnosis, overall mortality is a major concern. New technologies have attempted to look at breath volatile organic compounds (VOCs) detection to diagnose cancer. Gas Chromatography and Mass Spectrometry (GC - MS) have remained the gold standard of VOC analysis for decades, but it has limitations in differentiating VOCs between cancer subtypes. To increase efficacy and accuracy, new methods to analyze these breath VOCs have been introduced, such as Solid Phase Microextraction/Gas Chromatography-Mass Spectrometry (SPME/GC-MS), Selected Ion Flow Tube - Mass Spectrometry (SIFT-MS), Proton Transfer Reaction - Mass Spectrometry (PRT-MS), Ion Mobility Spectrometry (IMS), and Colorimetric Sensors. This article highlights new technologies that have been studied and applied in the detection and quantification of breath VOCs for possible cancer diagnoses.

Fake drugs: Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medications.

An estimated 30-70% of available medications in low-income countries and conflict states are of low quality or counterfeit. Reasons for this vary but most are rooted in regulatory agencies being poorly equipped to oversee quality of pharmaceutical stocks. This paper presents the development and validation of a method for point-of-care drug stock quality testing in these environs. The method is termed Baseline Spectral Fingerprinting and Sorting (BSF-S). BSF-S leverages the phenomena that all compounds in solution have nearly unique spectral profiles in the UV spectrum. Further, BSF-S recognizes that variations in sample concentrations are introduced when preparing samples in the field. BSF-S compensates for this variability by incorporating the ELECTRE-TRI-B sorting algorithm, which contains parameters that are trained in the laboratory using authentic, proxy low quality and counterfeit samples. The method was validated in a case study using fifty samples that include factually authentic Praziquantel and inauthentic samples prepared in solution by an independent pharmacist. Study researchers were blinded to which solution contained the authentic samples. Each sample was tested by the BSF-S method described in this paper and sorted to authentic or low quality/counterfeit categories with high levels of specificity and sensitivity. In combination with a companion device under development using ultraviolet light emitting diodes, the BSF-S method is intended to be a portable and low-cost method for testing medications for authenticity at or near the point-of-care in low income countries and conflict states.

A systematic review of various pKa determination techniques.

The pKa values of functional groups is crucial in determining the pharmacokinetic properties of a drug, affecting its absorption and thus bioavailability. This physicochemical property is also vital for the designing of drug excipients and vehicles. There are currently 13 known methods of determining a pKa value, namely: potentiometric titration, spectrometry, fluorometry, NMR, HPLC, conductometry, electrophoresis, voltammetry, solubility, partition coefficient, calorimetry, computational, and surface tension. Some of these techniques are more widely utilized and well-established compared to others, with each having their inherent advantages and disadvantages. This review discusses each of the aforementioned techniques with emphasis on their pros and cons.

Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications.

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients' quality of life with chronic diseases are discussed.

Alzheimer's disease failed clinical trials.

Alzheimer's disease is a progressive neurodegenerative disease typically presenting with symptoms of memory loss and cognitive decline. Existing theories for the causation of this focuses on amyloid beta plaques and neurofibrillary tau tangles. Most US Food and Drug Administration approved therapies for Alzheimer's disease target cognitive function. A multitude of clinical trials, with a variety of different targets have been conducted over the decades which have focused on the two clinical signs, with the only success being the controversial 2021 approval of an IgG1 anti-Ab antibody targeting the clearance of the Aß plaques. Presented is a review of all previously failed Alzheimer's disease clinical trials and the rationale for their failures.

Anti-obesity weight loss medications: Short-term and long-term use.

As obesity prevalence increases, more and more drugs that assist with weight loss have been developed. Numerous weight loss drugs had been approved, but many have also been withdrawn based on their lack of efficacy as well as safety concerns. Initial approaches in developing weight loss drugs was by increasing physiological energy expenditure and suppressing the appetite. Subsequently, as more physiological mechanisms for weight gain has been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied, and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues-such as adipose tissue or muscle-to promote weight loss, however to-date nothing has carried on into clinical practice. Starting with a brief history of early obesity treatments, this review evaluates current weight loss pharmaceutical options based on their duration of therapy status.

Beneficial effects of non-herbal supplements on patients with diabetes.

BACKGROUND AND AIMS: Controlling glycemic levels is crucial for patients with diabetes mellitus to improve their disease management and health outcomes. Beyond lifestyle modification and pharmacotherapy, some supplements have been shown to lower blood glucose as well as mitigate diabetic complications. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Only original human trials were used, and those published within the past two decades were primarily chosen. However, background information may contains review articles. RESULTS: Some non-herbal supplements have been suggested to lower fasting blood glucose, postprandial glucose, glycated glucose (HbA1c), lipid profiles, oxidative stress, and inflammation, as well as improving body composition, insulin sensitivity, blood pressure, and nephropathy. CONCLUSION: This review discusses ten non-herbal supplements that have been reported to have beneficial effects among different types of patients with diabetes as well as potential future clinical application. However, more long-term studies with a larger amount and more diverse participants need to be conducted for a robust conclusion. Also, mechanisms of action of antidiabetic effects are poorly understood and need further research.

Non-Invasive Breath Analysis for Disease Screening and Diagnoses.

Lower respiratory infections are a deadly communicable disease ranked as the fourth leading cause of death globally, with nearly 2 [...].

Non-invasive ways of administering insulin.

BACKGROUND AND AIMS: Insulin is crucial in the management of diabetes. However, requires injection which itself comes with some challenges. Alternative delivery routes have been investigated that are needle-free, with enhanced absorption and bioavailability. This review presents novel non-invasive insulin administration approaches that overcome some hurdles, as well as delineating their advantages and disadvantages. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Articles were evaluated between 1958 and 2022. An introductive approach was used to identify matters related to the concept of different ways of administering insulin. RESULTS: Approaches aim to administer insulin in a safe, stable, and easy to use form, whether via oral, buccal, intranasal, oral inhalation, transdermal, ocular, rectal, or vaginal routes. Some have been shown to clinically improve blood glucose levels, while others are still in the investigational stage. CONCLUSION: Many approaches have been taken in an attempt to overcome physical barriers of insulin delivery. Some of these systems discussed may reach the market in the future and assist the millions of people who currently take subcutaneous injections of insulin.

Impact of chronic obstructive pulmonary disease, lung infection, and/or inhaled corticosteroids use on potential risk of lung cancer.

Chronic obstructive pulmonary disease is the 3rd leading cause of death worldwide. It not only affects current and former smokers, but non-smokers as well. Chronic inflammatory response in this disease state leads to the production of genotoxic free radicals and reactive oxygen species that could result in tumorigenesis. Inhaled corticosteroids are used for the management of inflammation in patients experiencing frequent exacerbation and/or have a high eosinophil count. However, these steroids are often prescribed off-label for symptom management. Using inhaled corticosteroids to combat inflammation in chronic obstructive pulmonary disease patients is suggested to be protective against lung cancer. However, immunomodulatory effects of these medications can pre-dispose patients to develop respiratory infections such as tuberculosis or pneumonia. These lung infections have shown to also increase the risk of developing lung cancer. Since chronic obstructive pulmonary disease is an independent risk factor for developing lung cancer, a subsequent infection could have an additive effect. Additionally, the aforementioned chemo-preventive effects of inhaled corticosteroids are inconsistent due to there being limited data on the long term effects of using inhaled corticosteroids in patients who do not meet the treatment recommendation guidelines. Hence, it is necessary to recognize the indirect connection between inhaled corticosteroids and lung cancer possibly via lung infections in chronic obstructive pulmonary disease patients. The rationale behind this review is to better understand the mechanistic links that connect these multiple disease states which could aid in guiding treatment with inhaled corticosteroids in specific sub-groups. This review discusses possible pathways that could lead to the lung carcinogenesis and the cumulative impact of chronic obstructive pulmonary disease, inhaled corticosteroids use, and pulmonary infections on the risk of lung cancer.

Retinol binding protein 4 antagonists and protein synthesis inhibitors: Potential for therapeutic development.

Retinol-binding protein 4 (RBP4) is a serum protein that transports Vitamin A. RBP4 is correlated with numerous diseases and metabolic syndromes, including insulin resistance in type 2 diabetes, cardiovascular diseases, obesity, and macular degeneration. Recently, RBP4 antagonists and protein synthesis inhibitors are under development to regulate the effect of RBP4. Several RBP4 antagonists, especially BPN-14136, have demonstrated promising safety profiles and potential therapeutic benefits in animal studies. Two RBP4 antagonists, specifically tinlarebant (Belite Bio) and STG-001 (Stargazer) are currently undergoing clinical trials. Some antidiabetic drugs and nutraceuticals have been reported to reduce RBP4 expression, but more clinical data is needed to evaluate their therapeutical benefits. As regulating RBP4 levels or its activities would benefit a wide range of patients, further research is highly recommended to develop clinically useful RBP4 antagonists or protein synthesis inhibitors.

Benefits of delivering research podium presentations by students enrolled in pharmacy programs: A descriptive study.

INTRODUCTION: Objectives include (1) To create an opportunity for students enrolled in pharmacy programs to enhance their presentation skills by delivering research podium presentations at a regional conference; (2) To probe students' experience about podium presentations at the inaugural American Association for the Advancement of Science Pacific Division (AAAS PD) - American Association of Colleges of Pharmacy Students' Symposium; and (3) To introduce student pharmacists to science-oriented research. METHODS: The student presenters were asked to anonymously answer 15 questions before and after the symposium. Question topics included factual information about students' background and favorability perceptions about symposia. Scores were compared between pharmacy students and non-pharmacy students, and favorability ratings were compared before and after the symposium. RESULTS: Thirteen students delivered their podium presentations at the symposium entitled "Pharmaceutical Research and Development: From Bench to Patient-Centered Care" that was held in Pomona, California at the 99th Annual Meeting of the AAAS PD in 2018. Pharmacy and non-pharmacy students provided similar responses on favorability perceptions. Post-symposium perceptions were more favorable towards symposia compared to pre-symposium scores. CONCLUSIONS: Favorability scores revealed a positive perception of the event and what it offered in terms of scientific benefits, networking opportunities, and enhancing soft skills. Participating students had the chance to (1) prepare and independently deliver a podium presentation on pharmacy-related research topics at a regional meeting; (2) network and learn from each other and professionals in the audience about pharmacy research; and (3) practice soft skills such as communication, time-management, teamwork, scientific writing, and presentation skills.

Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies.

Photodynamic therapy is one of the more unique cancer treatment options available in today's arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers' transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.

Tachykinin NK2 antagonist for treatments of various disease states.

Tachykinin NK2 receptors are distributed in periphery, in the smooth muscle of the respiratory, gastrointestinal, genitourinary tract, and within the brain. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) are endogenous ligands for NK2 receptors and are active in the peripheral and central nervous systems. NK2 antagonists have the potential to reduce airway motor responses and prevent hyperactivity by inhibiting NKA-induced bronchoconstriction in asthmatic patients. Due to its abundance, peripherally and centrally, tachykinin NK2 receptor antagonists have high potential in treating various disease states ranging from asthma to irritable bowel syndrome, to detrusor hyperactivity, to anxiety. This review is an evaluation of NK2 receptor antagonists as possible therapeutics for a myriad of pharmacological treatments.

The increasing trend of Type 2 diabetes in youth: An overview.

INTRODUCTION: Pediatric Type 2 Diabetes Mellitus (T2DM) is increasing in incidence, largely in correlation with global childhood obesity crisis. COMPLICATIONS: Early detection and treatment are vital as diabetes has been shown to progress rapidly and aggressively amongst children. ETIOLOGY: Higher than expected insulin levels compared to adults, leads to more rapid ß cell decline. TREATMENTS: New treatments to control glycemic levels among youth with T2DM are being evaluated. This review summarizes the current understanding of causes, complications, and treatments for youth diagnosed with T2DM. OR. Pediatric Type 2 Diabetes Mellitus (T2DM) is increasing in incidence, largely in correlation with the global childhood obesity crisis. With increase in cases comes new challenges for medical professionals. Early detection and treatment are vital as the disease has been shown to progress aggressively and bring complications to children at a rapid rate. New treatments are currently being studied to control glycemic levels among youth with T2DM, as current options are not as effective chronically in children as in adults. This review summarizes the current understanding of causes, complications, and treatments for youth diagnosed with T2DM.

Current progress in pharmacogenomics of Type 2 diabetes: A systemic overview.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a prevalent disease with incidences increasing globally at a rapid rate. The goal of T2DM treatment is to control glucose levels and prevent the aggravation of glycemic symptoms. TREATMENT OPTIONS: T2DM regimen include metformin as the first-line, with sulfonylurea, thiazolidinedione (TZD), GLP-1, DPP4I, and SGLT2 inhibitor as the second-line treatment options. However, even with a multitude of choices, patient-to-patient variability due to pharmacogenomic differences still prevail. CONCLUSION: This review aims to discuss the responses of the major T2DM medications influenced by pharmacogenomics and investigate improved personalized therapy for T2DM patients.

Evaluating the mechanisms of action and subcellular localization of ruthenium(II)-based photosensitizers.

The identification of ruthenium(II) polypyridyl complexes as photosensitizers in photodynamic therapy (PDT) for the treatment of cancer is progressing rapidly. Due to their favorable photophysical and photochemical properties, Ru(II)-based photosensitizers have absorption in the visible spectrum, can be irradiated via one- and two-photon excitation within the PDT window, and yield potent oxygen-dependent and/or oxygen-independent photobiological activities. Herein, we present a current overview of the mechanisms of action and subcellular localization of Ru(II)-based photosensitizers in the treatment of cancer. These photosensitizers are highlighted from a medicinal chemistry and chemical biology perspective. However, although this field is burgeoning, challenges and limitations remain in the photosensitization strategies and clinical translation.

Glucagon delivery - An overview of current and future devices.

Glucagon is crucial in the treatment of Type 1 diabetes mellitus due to the prevalence of hypoglycemia in patients with this disorder. Hypoglycemia can be life-threatening, leading to loss of consciousness, and requiring emergency glucagon to reverse the effects. Emergency kits are difficult to use, requiring reconstitution of glucagon, which itself is not stable for lengthy periods. Approaches have aimed to improve stability which has allowed for use in pens or pumps. Glucagon can now also be delivered intranasally. This review discusses the history of glucagon, its current delivery methods as well as some modern approaches being introduced.