New Class Of Drugs Research Articles

Inhibition of fractalkine signalling in patients with acute myocardial infarction - First results from the FRACTAL trial

Abstract Background We have previously demonstrated a strong association between expression of the fractalkine receptor CX3CR1 on lymphocytes and microvascular obstruction (MVO) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. Our pre-clinical studies also found an improvement in infarct size, inflammation and intramyocardial haemorrhage (IMH) when rats were pre-treated with the fractalkine inhibitor KAND567. Purpose FRACTAL (FRACTalkine inhibition in Acute myocardial infarction) study was a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. Its primary aim was to assess the safety and tolerability of intravenous and oral administration of the fractalkine inhibitor KAND567 as well as reducing signs of reperfusion injury in STEMI patients undergoing PPCI. Methods Patients with a new diagnosis of anterior STEMI, who had index chest pain within 5 hours and angiographic occlusion of the LAD, were randomised on a 1:1 basis to receive either KAND567 or placebo over a period of 72 hours. All patients then underwent a baseline MRI scan at 3 days with a follow-up scan at 3 months, paralleled by longitudinal deep immuno­phenotyping over 9 time points. Results A total of 71 patients were enrolled into the study with 64 (90.1%) being male patients. The mean age of patients was 59.2 years. 37 patients received KAND567, whilst 34 received placebo over 72-hour period. Throughout the 3-month follow-up period, 23 (62%) patients from the KAND567 arm as compared to 24 (71%) patients in the placebo arm had reported adverse events. There was no statistical difference in serious adverse events (SAEs) between both arms with 9 documented in the placebo arm and 12 in the KAND567 arm. Safety bloods also demonstrated no significant differences between the two groups across all time points. There was a higher incidence of left ventricular (LV) thrombus in the placebo arm as compared to the KAND567 arm (17.6% vs. 2.7%; p=0.049). Additionally, the study also demonstrated a lower occurrence of IMH in the KAND567 arm compared to the placebo arm (35.5% vs. 55.2%; p=0.19). Deep immunephenotyping suggested clear target engagement in the KAND567 arm in natural killer cells as well as in cytotoxic T-lymphocytes. Conclusion This first in-man study demonstrates that inhibition of the fractalkine pathway in STEMI patients appears safe and well-tolerated, while demonstrating a promising potential in preventing LV thrombus and IMH. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase III study.LV thrombus and IMH

Is it Time for Multi-Drug Therapy with Combination of Therapeutic Nucleic Acids?

Therapeutic nucleic acids (TNAs) are a new class of drugs that exhibit different properties and mechanisms of action from those of small molecules or biological drugs. Over twenty oligonucleotide drugs and several COVID-19 vaccines have received regulatory approval for clinical use. A characteristic feature of these TNAs is that they are directed against one specific biological target and one specific RNA or DNA sequence. Consequently, TNAs currently used are administered as monotherapy. Due to the known advantages of multidrug therapy with low molecular weight drugs, it may be time to intensify work on such a treatment protocol, also in the case of TNAs.

A novel immunopharmacological biocompound

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

Computationally Driven Discovery and Characterization of SIRT3-Activating Compounds that Fully Recover Catalytic Activity under NAD+ Depletion

Many chronic, age-related disorders could be mitigated by enhancing the activity of enzymes that regulate biochemical signaling pathways, but all known modes of enzyme activation rely on allosteric binding sites, which have only been identified in less than 10% of proteins. Sirtuins (SIRT1-7) are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases playing critical roles in lifespan and age-related diseases. The physiological importance of sirtuins and the reduction in their catalytic activity with the age-related decline in NAD+ levels have stimulated intense interest in designing sirtuin-activating compounds; however, except for substrate-specific allosteric SIRT1 activators, methodologies for rational design of sirtuin-activating compounds are lacking. Here, we introduce methods for the activation of such enzymes that do not rely on allosteric binding sites, and we demonstrate their successful application to the discovery of first-in-class activators of sirtuin enzymes. We establish how all-atom simulations of an enzyme’s active site under the potential of a small molecule modulator can be used to identify molecular properties that achieve desired changes in local enzyme conformational degrees of freedom conducive to the enhancement of catalytic activity. We apply computational high-throughput screening based on this biophysical model for activation of sirtuin enzymes to the major mitochondrial sirtuin SIRT3, which plays a critical role in age-related disorders but does not have a known allosteric site; we thereby identify first-in-class, nonallosteric activators of this enzyme. These compounds are the first reported steady-state activators of the major mitochondrial sirtuin enzyme, and they operate according to a mode of action not shared by any existing drug. Two such compounds can almost double the catalytic efficiency of SIRT3 with respect to NAD+, thus compensating for the loss in SIRT3 activity that occurs due to the age-related decline in NAD+, and they may be developed for therapeutic applications to combat multiple types of age-related disorders. These discoveries establish a foundation for the development of a new class of drugs that function through the activation of enzymes by modulation of local conformational ensembles. Published by the American Physical Society 2024

Phytocannabinoids restore seizure-induced alterations in emotional behaviour in male rats.

Epilepsy often presents with severe emotional comorbidities including anxiety and abnormal fear responses which impose a significant burden on, and reduce, quality of life in people living with the disease. Our lab has recently shown that kindled seizures lead to changes in emotional processing resulting from the downregulation of anandamide signalling within the amygdala. Phytocannabinoids derived from the Cannabis sativa plant have attracted a lot of interest as a new class of drugs with potential anticonvulsant effects. Among the wide number of compounds occurring in Cannabis sativa, Δ9- tetrahydrocannabinol (THC), the one responsible for its main psychoactive effects, and the nonpsychoactive cannabidiol (CBD) have been extensively examined under pre-clinical and clinical contexts to control seizures, however, neither have been assessed in the context of the management of emotional comorbidities associated with seizure activity. We used two behavioural procedures to assess anxiety- and fear-like responding in adult male Long-Evans rats: elevated plus maze and auditory fear conditioning. In agreement with previous reports, we found seizure-induced increases in anxiety- and fear-like responding. These effects were reversed by either CBD (vaporized) or THC (oral). We also found that antagonism of serotonin 1 A receptors prior to CBD exposure prevented its protective effects. Phytocannabinoids offer a novel and reliable opportunity to treat seizure induced comorbid emotional alterations.

The role of P-CABs in GERD.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors (PPIs). The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease (GERD). Multiple clinical trials have compared P-CABs with PPIs in erosive esophagitis. Additional trials have compared P-CABs with placebo in non-erosive reflux disease. Relevant results are reviewed and inferences drawn for their use in the US. Lastly, consideration is given to additional, potential uses of P-CABs in the broader spectrum of GERD and some suggestions made for future research initiatives.

Les cellules CAR-T anti-CD19 : prototypes du médicament vivant

Chimeric antigen receptors (CARs) are synthetic receptors that determine the specificity and functions of transduced T cells. They bind cell surface antigens through their extracellular domain and initiate via their intracellular domain cytolytic functions, cytokine secretion and proliferation. The CAR thus specifies the properties of a living drug that is programmed to exert anti-tumor and immunoregulatory effects.After establishing a method to stably integrate foreign genes in primary T lymphocytes in the early 1990s, we identified combinatorial signaling modules that could sustain a prolonged T cell function [17], which underpins an essential feature of a living drug. We further identified CD19 as a promising molecular target, which, based on encouraging preclinical results in mice [30], paved the way for clinical trials.The first clinical studies in patients with relapsed, refractory leukemias and lymphomas, which all made use of CAR T cells produced in the academic setting, yielded remarkable clinical response that were soon confirmed at several centers [2]. CAR T cells targeting CD19 were the first living drugs to be approved by the US Food and Drug Administration in 2017 and the European Medicines Agency in 2018.CD19 CARs have thus spawned a new class of drugs and inspired new applications to treat cancer and autoimmune diseases with engineered immune cells, warranting sustained efforts to lower their cost and increase their availability in equitable fashion.

Oleanolic acid derivatives against drug-resistant bacteria and fungi by multi-targets to avoid drug resistance

Mixed infections caused by drug-resistant bacteria and fungi pose a severe threat to human health, and multi-target drugs may provide an effective approach to combat drug-resistant pathogens. Therefore, this study aimed to investigate the efficacies of some oleanolic acid (OA) derivatives against multidrug-resistant (MDR) bacteria and fungi using in vitro and in vivo experiments. Novel amphiphilic OA derivatives were designed and optimised, in which compounds G1 and J1 exhibited effective antimicrobial activity (MICs = 1–2 μg/mL), high selectivity against MDR strains, rapid bactericidal activity, and good predictive pharmacokinetics. Mechanistically, both compounds prevented drug resistance by disrupting the bacterial cell membrane, inserting into the DNA, and binding to DNA gyrase. Additionally, J1 reduced microbial count in a mouse MRSA skin infection model and accelerated wound healing much better than vancomycin. Conclusively, this study presents a new class of potential drugs for resistant bacteria and fungi.

Equine metabolic investigation of the phosphodiesterase-4 inhibitor ibudilast as a potential performance enhancer.

Phosphodiesterase 4 (PDE4) inhibitors are a newer class of drugs that induce bronchodilation and have anti-inflammatory effects, making them susceptible to misuse as performance enhancers in competitive sports. This study explores the metabolic conversion of PDE4 inhibitor ibudilast in thoroughbred horses after oral administration and in vitro using equine liver microsomes and Cunninghamella elegans. A liquid chromatography-high resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of 20 in vivo metabolites were identified under experimental conditions, including 12 Phase I and 8 Phase II conjugated metabolites. Phase I metabolites were predominantly formed through hydroxylation (mono-, di-, and tri-hydroxylation). Demethylated metabolites were also identified during this investigation. Additionally, the research detected Phase II metabolites conjugated with glucuronic and sulfonic acids. The data presented here can assist in detecting the PDE4 inhibitor ibudilast and uncover its illicit use in competitive sports.

Update on Sodium Glucose Cotransporter Type 2 Inhibitors Use in Kidney Transplant Patients

Sodium glucose cotransporter type 2 inhibitors are a new class of drugs that act on the cardiovascular system, kidneys and metabolism in a multiple ways. Indeed, even though their principal action involves the transport of sodium and glucose in the convoluted distal tubule, they have multiple actions, such as antifibrotic and endothelial protective effects. Their principal mechanism consists of the loss of sodium and glucose. Therefore, they affect blood pressure and glucose metabolism. Their first use was in the diabetic general population; later, some studies documented their activity in the nondiabetic general population and in heart failure in chronic kidney disease patients. Only in recent years have several small studies documented the efficacy of these drugs in diabetic and nondiabetic kidney transplant patients; relatively large studies are rare, very recent, and open new routes for the development of these drugs.

Long-Term Safety and Efficacy of Janus kinase (JAK) Inhibitors in the Treatment of Rheumatoid Arthritis

Background: Janus kinase (JAK) inhibitors are a new class of drugs for the treatment of rheumatoid arthritis (RA); however, the long-term consequences of using these drugs are still not well understood. Objective: The primary objective of this research was to examine the effectiveness and safety of JAK inhibitors for the management of rheumatoid arthritis (RA) patients. Methodology: Clinical raw data of 150 RA patients receiving JAK inhibitors was collected in different tertiary care hospitals in Lahore, Pakistan from March 2023 to June 2024. till were conducted. The anti-inflammatory effect was evaluated by the Disease Activity Score in 28 joints (DAS28) and the safety profile through adverse events, laboratory markers, and patients self-reported outcomes. The SPSS version 27 applied for raw data analysis which used the paired t-tests and multiple regression models to establish the factors that determine favorable outcomes and complications. Results: JAK inhibitors also reduced the DAS28 scores from baseline to 24 months by a mean of 3. 2 ± 1. 1 (p<0. 001). The findings stated that 12 percent of the patients at baseline and 45 percent of the patients at 24 months had achieved remission. The reported side effects were infections, 25%; gastrointestinal problems, 18%; and abnormal liver function tests, 10%. Severe adverse reactions were noted in 5% of the patients and no new safety issues were observed over the course of the treatment. Conclusion: JAK inhibitors have been shown to be useful in decreasing the activity of RA for the long-term use with reasonable side effects. The results provided evidence that JAK inhibitors were best treatment of rheumatoid arthritis (RA) but for best efficacy results closely monitoring and specific approach should be applied.

Molecular diagnostics of familial hypercholesterolemia in Russia: yesterday, today and tomorrow

Familial hypercholesterolemia is a severe hereditary disease leading to the development of atherosclerosis and its complications in the form of angina pectoris, myocardial infarction, cerebral stroke, or even leading to sudden death. Since the description of the disease, the concept of it has undergone significant evolution. First, it became clear that the prevalence of this disease was significantly higher than originally thought (1:300 for heterozygous familial hypercholesterolemia and not as 1:500 as estimated earlier). Secondly, it has been established that it is not based on the pathology of the low-density lipoprotein receptor gene alone, but includes at least four monogenic forms (defects of the APOB, PCSK9, ARH genes) and may also have a multigenic nature. Thirdly, with the development of DNA analysis methods from the initially available Southern hybridization to next generation DNA sequencing, the exceptional molecular heterogeneity of familial hypercholesterolemia became obvious and, accordingly, the need to establish national spectra of mutations leading to the development of familial hypercholesterolemia was established. Researchers have moved from characterizing individual mutations to creating national registries and databases. Finally, research into the genetics of familial hypercholesterolemia has led to the emergence of new classes of cholesterol-lowering drugs. In Russia, molecular diagnostics of familial hypercholesterolemia has also undergone significant changes since the beginning of the study of familial hypercholesterolemia in 1987 and to the present, consideration of these changes formed the basis of this review.

The Analysis Study of Effects of Glucagon-Like Peptide-1 Receptor to Reduce Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: A Comprehensive Systematic Review

Background: The aim of this study to show about effects of glucagon-like peptide-1 receptor to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. Result: Eight publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: GLP‐1 receptor agonists represent a relatively new class of drugs used for the treatment of T2DM. They are not only able to improve hyperglycaemia of diabetic patients but also directly influence in addition other significant risk factors for CVD such as high blood pressure, dyslipidaemia or obesity. These properties explain at least in part the positive results of the CV outcome studies for liraglutide, semaglutide, dulaglutide and albiglutide, all of which showed not only CV safety but also an improvement in CV prognosis.

2023 ESC guidelines for management of cardiomyopathies: short review with implications for the clinical practice in Bulgaria

The 2023 European Society of Cardiology guidelines for the management of cardiomyopathies (CM) provide practical recommendations for diagnosis and treatment. They emphasize on the need for a systematic clinical evaluation beginning with clinical suspicion of CM and using a multiparametric approach that leads to classification of CM into one of five distinct phenotypes. А cardiomyopathy mindset, together with a multidisciplinary approach are crucial. Further investigations, including advanced imaging and genetic testing, are needed to make a phenotype-based etiological diagnosis. Detection of pathogenic genetic variants allows risk stratification of sudden cardiac death, where new recommendations are available regarding primary prevention. Therapeutic options are expanded with the approval of a new class of drugs for the treatment of symptomatic hypertrophic cardiomyopathy with left ventricular outflow tract obstruction. Specific exercise recommendations are given and reproductive issues in patients with CM are addressed. The lack of reimbursement by the National Health Insurance Fund (NHIF) of genetic testing and the severely limited reimbursement of some imaging methods are a significant problem in Bulgaria, which leads to difficulties in implementing the new guidelines.

The metastatic and advanced upper tract urothelial carcinoma-a separate entity or bladder cancer's younger sibling?

Upper tract urothelial carcinoma (UTUC) is acancer that is often already in an advanced stage at the time of initial diagnosis. Although urothelial carcinoma of the upper and lower urinary tracts both originate from the urothelium and have similar genetic alterations, there are significant differences in their distribution. In localized high-risk UTUC, radical nephroureterectomy is the gold standard therapy. In metastatic UTUC, major changes are emerging in sequential therapy due to the investigation of new classes of drugs. In addition to platinum-based combination chemotherapy and immunotherapy, new substances such as antibody-drug conjugates (ADCs) and FGFR inhibitors are used.

Rimegepant - a breakthrough drug for migraine treatment - literature review

Migraine is a chronic condition that manifests itself periodically. It is characterized by recurrent, severe, often hemiplegic, throbbing headaches accompanied by autonomic symptoms in the form of nausea, vomiting, hypersensitivity to noise and light. For many years, triptans have been the gold standard in the treatment of migraine, acting by constricting blood vessels and inhibiting the release of neuropeptides. However, their efficacy is not satisfactory for all patients, especially those with cardiovascular disease. In response to the need for effective and safe therapies, gepants, a new class of drugs that block the calcitonin gene-related peptide (CGRP) receptor, have emerged. Rimegepant, one of the newest representatives of gepant, has been approved for the treatment of migraine both in the acute attack phase and prophylactically. Clinical trials have shown its effectiveness in reducing the number of days with migraine and alleviating associated symptoms. Rimegepant also has a favorable safety profile, making it a promising therapeutic option for migraine patients. This article aims to discuss in detail rimegepant as a new treatment option for migraine, including its mechanism of action, efficacy, safety profile, clinical trial and outlines the benefits of introducing this drug into standard clinical practice.

Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells.

The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the SKOV-3 human OCC. Treatment with Con-3 and Con-7, but not with their unconjugated GnRH counterparts, resulted in the accumulation of mitoxantrone within the SKOV-3 cells, increased their apoptosis, and reduced their proliferation, in a dose- and time-dependent manner, with half-maximal inhibitory concentrations of 0.6-0.9 µM. It is concluded that Con-3 and Con-7 act as cytotoxic "prodrugs" in which mitoxantrone is delivered in a GnRH-R-specific manner and constitute a new class of lead compounds for use as anticancer drugs targeting ovarian tumors.

Patterns of Transmitted Drug Resistance Mutations and HIV-1 Subtype Dynamics in ART-Naïve Individuals in Veneto, Italy, from 2017 to 2024.

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017-2019 to 15.5% in 2020-2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

The novel peptide PEP-Z-2 potentially treats renal fibrosis in vivo and in vitro by regulating TGF-β/Smad/AKT/MAPK signaling

Renal fibrosis is a process in which excessive deposition of extracellular matrix leads to an increase in tissue hardness and gradual destruction of the renal parenchyma. Chronic kidney disease (CKD) commonly progresses to end-stage renal disease (ESRD), ultimately leading to renal failure. This disease has high incidence and mortality rates, but to date, effective treatment options are lacking. PEP-Z-2 is a collagen peptide isolated from redlip croaker scales and may have potential fibroprotective activity. In this study, PEP-Z-2 was found to alleviate unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced kidney injury in a mouse model, reduce collagen deposition in tissues, normalize renal function, reduce the expression of fibrosis markers, reduce reactive oxygen species (ROS) production, and restore the balance of the oxidant/antioxidant system. In vitro experiments also demonstrated that PEP-Z-2 inhibits the TGF-β-induced differentiation of fibroblasts and renal tubular epithelial cells into myofibroblasts and reduces the production of extracellular matrix (ECM) proteins such as fibronectin, Col I, and α-SMA, demonstrating notable therapeutic effects on renal fibrosis. This effect is achieved by regulating the TGF-β/Smad/AKT/MAPK pathway. Our research suggested that PEP-Z-2 is a potential therapeutic drug for renal fibrosis, and peptides from aquatic organisms may constitute a new class of candidate drugs for the treatment of renal fibrosis and even other types of organ fibrosis.

Combatting Fungal Infections: Advances in Antifungal Polymeric Nanomaterials.

Fungal pathogens cause over 6.5 million life-threatening systemic infections annually, with mortality rates ranging from 20 to 95%, even with medical intervention. The World Health Organization has recently emphasized the urgent need for new antifungal drugs. However, the range of effective antifungal agents remains limited and resistance is increasing. This Review explores the current landscape of fungal infections and antifungal drugs, focusing on synthetic polymeric nanomaterials like nanoparticles that enhance the physicochemical properties of existing drugs. Additionally, we examine intrinsically antifungal polymers that mimic naturally occurring peptides. Advances in polymer characterization and synthesis now allow precise design and screening for antifungal activity, biocompatibility, and drug interactions. These antifungal polymers represent a promising new class of drugs for combating fungal infections.