Nystatin is a commonly used antifungal medicine for the treatment of candidiasis, particularly in superficial and mucosal infections. Its clinical usefulness is limited by poor water solubility, instability, a short residence time in the mucosa, and low absorption. This review critically evaluates 22 eligible studies (PRISMA 2020-compliant search, January 2004-December 2025) on nano- and microparticulate delivery systems for nystatin in the treatment of candidiasis, using a novel analytical framework that maps nanocarrier physicochemical properties to site-specific delivery requirements across oral, cutaneous, and vulvovaginal candidiasis. Nanoemulsions, nanosuspensions, Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), polymeric nanoparticles, and vesicular systems, specifically liposomes and nanocubosomes, are evaluated by standardized physicochemical parameters, evidence-graded antifungal endpoints, and a translational readiness evaluation. Nanoemulsions and NLCs demonstrate the most favorable translational profiles. Challenges related to manufacturing scalability, long-term stability, and regulatory acceptance remain barriers to clinical translation.

Nanotechnology has emerged as a transformative force in modern healthcare, particularly through the innovative use of nanobots for drug delivery. These microscopic, programmable devices are designed to navigate biological systems and deliver therapeutic compounds directly to targeted tissues or cells, thereby enhancing drug bioavailability and minimizing systemic side effects. This review explores recent advancements in nanobot technology, including their engineering with advanced materials, magnetic control systems, and programmable designs that enable precise, adaptable drug delivery. The implications of nanobots are profound, offering targeted interventions in oncology, neurology, and infectious diseases, along with the potential for personalized medicine and real-time monitoring of treatment. Despite the promising outlook, significant challenges remain in optimizing biocompatibility, propulsion mechanisms, and regulatory frameworks. This work highlights the need for interdisciplinary collaboration to refine nanobots' clinical applications and unlock their full potential in shaping the future of targeted therapeutic approaches.

MicroRNA (miRNA)-based therapeutics can modulate disease-associated gene networks by restoring protective miRNAs or inhibiting pathogenic miRNAs, yet clinical translation remains limited despite substantial preclinical progress. This review critically evaluates representative clinical and advanced translational programs, including Miravirsen, MRX34, Cobomarsen, Remlarsen, RGLS4326, and farabursen (RGLS8429), to compare molecular designs, delivery approaches, development outcomes, and translational bottlenecks. These programs show that clinical success cannot be explained by delivery efficiency alone, but depends on the interplay among tissue selectivity, intracellular delivery and endosomal escape, immune compatibility, sequence- and network-level pharmacology, PK/PD, and Chemistry, Manufacturing, and Controls (CMC). We also assess emerging strategies, including organ-selective lipid nanoparticles, stimuli-responsive nanocarriers, extracellularvesicle- based systems, and local delivery, with emphasis on their translational potential and remaining validation needs. Drawing on these lessons, we propose a Four-Pillar Framework integrating Delivery Systems, Immune Safety, CMC and Manufacturing Readiness, and biomarker-guided Clinical Design. Together, these principles support coordinated optimization across biological, pharmaceutical, and clinical dimensions rather than isolated improvement of individual delivery parameters.

Extracellular Vesicles (EVs) are active mediators of intercellular signaling in the Central Nervous System (CNS), operating alongside synaptic transmission as an extra form of wireless communication between neurons and other brain cell types. Their biocompatibility positions them as promising carriers for neurobiological therapeutics; however, translation hinges on clarifying when and how EVs traverse the Blood-Brain Barrier (BBB) and how their design can be aligned to pathophysiology. We synthesize evidence for BBB transport from in vitro models and in vivo visualization and functional studies and build on this foundation by outlining engineering strategies for CNS tropism both to the brain and within it. Across these areas, current advances remain largely siloed despite clear mechanistic interdependence, underscoring the need for standardized frameworks that integrate barrier biology, engineering design, and disease context. We argue that progress now depends on two fronts: developing preclinical models that accurately capture mechanisms governing bidirectional EV transport through the BBB and aligning vesicle design and delivery parameters with those mechanisms. Achieving this will require closer integration with biomarker discovery and greater standardization across preclinical workflows. Together, these steps chart a path from proof of concept to clinically adaptable EV therapeutics for CNS disease.

The blood-brain barrier (BBB) is critical in CNS pharmacotherapy; it blocks the entry of 98 per cent of small-molecule compounds and almost all macromolecules into the brain parenchyma via tight junction complexes, efflux transporter action, and enzymatic breakdown. This review focuses on the mechanistic basis of BBB resistance and analyses the current landscape of new drug delivery systems developed to overcome this barrier. We elaborate on polymeric nanocarriers, lipid-based nanocarriers, exosomes, dendrimers, and metallic nanoparticles, including surface engineering, the possibility of receptor-mediated transcytosis via transferrin, LRP1, and glucose transporter receptors, and known preclinical efficacy in glioblastoma, Alzheimer's disease, and Parkinson's disease. Non-invasive delivery through the nose is evaluated as intranasal delivery because it utilises olfactory and trigeminal receptors to circumvent systemic delivery. BBB modulation mediated by focused ultrasound is mentioned as one of the physical adjuncts to enhance CNS penetration. Clinical translation is poor, even where the preclinical data are positive. Most late-stage failures can be attributed to protein corona formation, anti-PEG immunogenicity, interpatient heterogeneity in the BBB, and manufacturing scalability. These obstacles are critically evaluated with the help of recent clinical trial evidence, where preclinical models cannot be used as predictors of human outcomes. In the future, AI-based nanocarrier design, machine-learning-driven prediction of BBB permeability, and patient-centred nanomedicine platforms will provide a viable pathway to customised CNS therapeutic approaches. Multimodal strategies integrating RMT, stimuli-responsive carriers, and CRISPRbased gene delivery may collectively overcome the translational gap that single-platform approaches have consistently failed to bridge.

Polycystic Ovary Syndrome (PCOS) is a complex metabolic-reproductive condition, which is linked with a hormonal imbalance, ovarian dysfunction, insulin resistance, and chronic lowgrade inflammation. Although much research has been conducted over the years, there are no potential diagnostic methods, and existing therapies are symptomatic. Extracellular Vesicles (EVs), such as exosomes and microvesicles, are known to play a critical role in intercellular communication, are significant for reproductive signaling, metabolic regulation, and immune modulation, and are altered in PCOS. No thorough review has been conducted to date that brings together evidence regarding EVs in PCOS. These issues have been addressed separately in the past or in a narrow context with regard to vesicles of the follicular fluid. This review aims to report the association among EV biogenesis, molecular cargo, and the pathophysiological mechanisms underlying endocrine, metabolic, and inflammatory changes in PCOS. The paper is organized as follows: first, it describes the clinical complexity and unmet needs of PCOS, and then briefly describes EV biology. The paper then provides evidence supporting the hypothesis that dysfunctional EV signaling dysregulates granulosa and theca cells, leading to follicular arrest, the development of a dysmetabolic condition, endothelial cell destruction, and systemic inflammation. Biomarkers of EVs are discussed, including circulating markers, phenotypic markers, and the potential for monitoring disease response to treatment. Lastly, the article compares potential therapeutic breakthroughs, such as EVs derived from mesenchymal stem cells, engineered vesicles for targeted delivery, and emerging clinical evidence, and ends with preclinical and emerging clinical evidence. This review aims to facilitate the translation of mechanistic insights into clinical practice, thereby expediting the use of EVs as diagnostic biomarkers and therapeutic tools for diagnosing and treating PCOS.