Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice.

Fungal infections remain a major and growing global health concern, particularly in immunocompromised populations and in settings where antifungal resistance is increasing. Imidazole antifungals continue to play an important role in the treatment of superficial and mucocutaneous mycoses because they inhibit lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis. This mechanism disrupts fungal membrane integrity and underlies their clinical utility. However, the effectiveness of imidazoles is increasingly limited by resistance mechanisms such as CYP51 mutations, efflux pump overexpression, and biofilm-associated tolerance. In parallel, several biopharmaceutical constraints, including poor aqueous solubility, limited tissue penetration, short residence time, and variable local drug exposure, further reduce therapeutic performance. This review critically examines the medicinal chemistry, mechanism of action, and resistance biology of imidazole antifungals, while also highlighting the role of pharmacokinetic and pharmacodynamic limitations in treatment failure. Particular attention is given to emerging drug delivery approaches, including lipid-based systems, vesicular carriers, nanocarriers, and other advanced topical formulations, which are being developed to improve solubility, enhance tissue retention, and sustain antifungal exposure at the site of infection. By integrating resistance mechanisms with formulation science, the review provides a translational perspective on how imidazole antifungals may be optimized for improved clinical utility and resistance management.

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research.

Protein–protein interactions (PPIs) are critical for cellular signaling, apoptosis regulation, and immune function in the body, and dysregulation is a hallmark of cancer. The large, dynamic, and shallow nature of PPI interfaces rendered them “undruggable” by conventional small molecules in the past. Recent advances in structural biology, chemical innovation, and artificial intelligence have revolutionized the landscape of PPI-directed drug discovery. This review summarizes the mechanistic roles of PPIs in oncogenesis, critically discusses novel therapeutic interventions, such as small molecules, peptidomimetics, stapled peptides, proteolysis-targeting chimeras (PROTACs), molecular glues, and AI-based drug optimization strategies, altering the druggable proteome in oncology. Therapeutics with clinically well-validated action, including Venetoclax and AMG 510, and next-generation candidates demonstrate the translational applications of these approaches. Some of the key challenges, such as interface complexity, specificity, bioavailability, and resistance, are addressed together with countermeasures like rational design, combination therapies, enhanced delivery systems, and biomarker-based patient selection. To this end, the incorporation of multi-omics data and artificial-intelligence (AI)-driven modeling technologies is revolutionizing the personalized cancer therapeutics development space. Collectively, these advances mark a paradigm shift: PPIs, once considered inaccessible, are now at the forefront of precision oncology, offering new hope for patients with previously intractable malignancies.

Atopic dermatitis (AD) is a common chronic inflammatory condition of the skin that has increased dramatically over the past decade and significantly impacts individual quality of life. Corticosteroids are still the primary therapy for AD, but there are limitations to their continued use due to potential adverse effects, particularly when used in sensitive areas. Topical calcineurin inhibitors (CNIs), such as tacrolimus and pimecrolimus, are available as a safe, steroid-sparing alternative that directly inhibit calcineurin-mediated activation of T cells and have been shown to be efficacious according to varying clinical study designs including randomized controlled trials, registry studies and meta-analyses. Although there was controversy regarding the safety of CNIs subsequent to the FDA’s black-box warning in 2006, the preponderance of evidence supports their continued safety when used as directed. In contrast to biologics and JAK inhibitors, CNIs occupy an inherently unique therapeutic niche for use in pediatric patients, have demonstrated historical efficacy, and can provide localized affordable treatment in sensitive areas including the face, eyelids and intertriginous surfaces. Furthermore, the role of CNIs in the context of precision dermatology continues to be defined through new innovations including barrier-repair strategies used in combination with topical medications, microneedle systems, and nanocarrier formulations. Hence, the role of CNIs in the current AD treatment paradigm is crucial and lies at the interface between topical corticosteroids and systemic immunomodulatory agents. The narrative review discusses recent advances in formulation strategies, combination approaches, and targeted delivery systems, underscoring how CNIs continue to bridge established practice and emerging therapeutic innovation in AD.

Localized drug-delivery systems have attracted considerable attention in recent years owing to their ability to deliver therapeutic agents directly to the site of action, thereby achieving higher l...