BACKGROUND: Acute lung injury (ALI) is a pathological condition characterized by diffuse lung injury. Excessive macrophage polarization to the M1 type in lung tissue plays a crucial role in the incidence and aggravation...BACKGROUND: Acute lung injury (ALI) is a pathological condition characterized by diffuse lung injury. Excessive macrophage polarization to the M1 type in lung tissue plays a crucial role in the incidence and aggravation of ALI. RESEARCH DESIGN AND METHODS: Bilirubin (BR) has been applied as a therapeutic agent in various diseases due to its ability to regulate macrophage polarization. Based on the inherent engulfing of M1 macrophages toward xenobiotic nanomedicines, an inhalable BR nanomedicine was developed for the treatment of ALI. The BR nanoparticles (BRn) were first prepared using a one-step nanoprecipitation method, followed by surface modification with immunoglobulin G (IgG) at a 20% weight ratio to prepare BRn@IgG. RESULTS: Both nanoparticles exhibited excellent stability and enhanced antioxidative properties in aqueous phases. To gain the initiative, the IgG-modified nanoparticles could smartly bind to M1 macrophages, resulting in greatly improved BR delivery efficiency to macrophages and thus enhancing antioxidative, anti-inflammatory, and polarization-regulating effects compared to naked BRn. BRn@IgG evaded mechanical clearance from lung tissue and demonstrated prolonged retention in the pulmonary environment, thereby attaining the most potent therapeutic effect among all formulations in this study. CONCLUSION: BRn@IgG could be considered a novel and effective therapeutic agent for the ALI treatment.
INTRODUCTION: Viral diseases such as influenza, severe acute respiratory syndrome (SARS) caused due to coronaviruses (CoVs), Ebola, and acquired immunodeficiency syndrome (AIDS) caused due to human immunodeficiency virus...INTRODUCTION: Viral diseases such as influenza, severe acute respiratory syndrome (SARS) caused due to coronaviruses (CoVs), Ebola, and acquired immunodeficiency syndrome (AIDS) caused due to human immunodeficiency virus (HIV) are still some of the major global causes of morbidity and mortality. Traditional antiviral therapies face limitations because of resistance development and toxicity. As a result, plant-derived medicines are gaining more attention for their therapeutic potential, owing to their lower toxicity and reduced likelihood of resistance development. AREAS COVERED: This review critically examines the antiviral properties of phytoconstituents like coumarins, steroids, and polysaccharides against various viruses. It discusses their integration with nanotechnology delivery systems to overcome bioavailability issues and highlights the need for translational studies to corroborate in vitro results. EXPERT OPINION: The convergence of phytotherapy and nanotechnology represents a promising frontier in antiviral drug development. While significant progress has been made in identifying active phytochemicals and formulating them with nanocarriers, more data, clinical research, standardization efforts, and regulatory clarity are needed. This review may serve as a foundational resource for researchers aiming to develop innovative antiviral therapies based on natural compounds and nanotechnology-based delivery systems.
Kadamus C, Sibi S, Bharadwaj R
… +1 more, Subramony JA
Expert Opin Drug Deliv
· 2026 Feb · PMID 41384591
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INTRODUCTION: Translating preclinical findings in human neurological drug delivery remains a challenge, particularly for molecules administered directly into cerebrospinal fluid (CSF) via intrathecal, intracisternal, or...INTRODUCTION: Translating preclinical findings in human neurological drug delivery remains a challenge, particularly for molecules administered directly into cerebrospinal fluid (CSF) via intrathecal, intracisternal, or intracerebroventricular routes. Anatomical and physiological disparities between animal models and the human neuroaxis complicate extrapolation of pharmacokinetic and pharmacodynamic data. AREAS COVERED: This review synthesizes expert perspectives on translational barriers of CSF-mediated delivery. The review focuses on macroscopic aspects such as delivery methods, CSF flow, and neuroanatomical features, while remaining agnostic of specific drugs or injectates. While physiological processes such as neuronal uptake inform CNS biodistribution, they are drug-specific and beyond this review's scope.Using a hypothesis-driven framework, literature was analyzed and categorized into themes: Preclinical-to-Human Translation, Neuroimaging, and CSF Flow Characterization (Theoretical, Experimental, Clinical). Strategic approaches identified include leveraging neuroimaging technologies and adopting tiered, multi-species modeling to better approximate human CNS dynamics. The glymphatic system and parameters for enhancing parenchymal distribution are highlighted as promising pathways. We recommend integrative frameworks that combine imaging, modeling, and biological validation. EXPERT OPINION: We propose a roadmap emphasizing harmonized imaging and multimodal modeling to investigate CNS delivery modalities. These foundational steps are essential for bridging preclinical and clinical gaps and accelerating the development of next-generation CNS delivery platforms.
Hussein I, Krabicová I, Hoti G
… +4 more, Er-Rahmani S, Matencio A, Caldera F, Trotta F
Expert Opin Drug Deliv
· 2026 Mar · PMID 41355811
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INTRODUCTION: Cyclodextrin-based drug delivery systems provide a robust platform for designing targeted nanocarriers that efficiently encapsulate, stabilize, and deliver poorly soluble drugs to specific sites. Their uniq...INTRODUCTION: Cyclodextrin-based drug delivery systems provide a robust platform for designing targeted nanocarriers that efficiently encapsulate, stabilize, and deliver poorly soluble drugs to specific sites. Their unique ability to form host - guest complexes and construct supramolecular networks adorned with tailored ligands allows precise targeting of diseased areas, thereby enhancing therapeutic efficacy while minimizing systemic side effects. AREAS COVERED: This review provides an overview of recent advances in cyclodextrin-based carriers for targeted drug delivery. It examines a wide array of ligand-functionalized systems, from conjugates and assemblies to branched polymers and nanosponges, organized according to their target organs, including the brain, eyes, lungs, gastrointestinal tract, liver, and breast. The discussion is grounded in an extensive literature search, highlighting strategies such as the incorporation of active targeting ligands, stimuli-responsive release mechanisms, and dual-function theragnostic platforms. EXPERT OPINION: Although cyclodextrin-based systems have demonstrated promising improvements in drug solubility, stability, and target specificity, challenges remain with regard to overcoming biological barriers and minimizing off-target effects. The authors believe that continued optimization of carrier design, combined with advances in targeting and stimuli-responsive technologies, will be crucial for translating these innovative systems into effective clinical therapies.
INTRODUCTION: This review summarizes the application of nanomaterial-mediated intra-articular targeted drug delivery systems in the treatment of osteoarthritis (OA) and their regulatory mechanisms on key cellular signali...INTRODUCTION: This review summarizes the application of nanomaterial-mediated intra-articular targeted drug delivery systems in the treatment of osteoarthritis (OA) and their regulatory mechanisms on key cellular signaling pathways. Studies have shown that novel nanocarriers can effectively load, deliver, and controllably release therapeutic agents, significantly enhancing drug bioavailability and reducing systemic toxicity. By precisely modulating signaling pathways, nanomaterials (NM) can effectively suppress inflammatory responses, alleviate oxidative stress, promote chondrocyte anabolism, delay extracellular matrix degradation, and regulate programmed cell death. This study highlights the potential of NM as a multi-target, synergistic therapeutic strategy for OA intervention, providing a theoretical and experimental basis for the development of next-generation precision therapies for OA. AREAS COVERED: This paper reviews the research progress of nano-drug delivery technology in the treatment of joint diseases, focusing on the potential mechanisms of targeted drug delivery and retention, promoting regeneration and repair, and realizing anti-inflammatory and antioxidant effects. We identified relevant literature through PubMed and Web of Science, focusing on studies published over the past five years. EXPERT OPINION: Nanomaterials for osteoarthritis treatment are evolving from passive drug carriers to intelligently responsive, targeted multifunctional systems capable of personalized, proactive, and regenerative therapy, overcoming current limitations in toxicity and delivery precision.
INTRODUCTION: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with conventional therapies mainly providing symptomatic relief without targeting underlying molecular and cellular mechanisms. A...INTRODUCTION: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with conventional therapies mainly providing symptomatic relief without targeting underlying molecular and cellular mechanisms. Additionally, limitations of systemic drug administration, including poor tissue targeting and low accumulation, highlight the need for innovative approaches. AREAS COVERED: Nanomedicine offers promising strategies for CVDs. Among nanocarriers, calcium phosphate nanoparticles (CaP NPs) are particularly attractive due to their biocompatibility, biodegradability, pH-responsive behavior, and versatility for drug incorporation. This report summarizes recent advances, identified through a literature search using Web of Science, PubMed and Scopus, on the application of CaP NPs for CVD therapy. Although still in its infancy, emerging evidence, including studies in large animal models, suggests the CaP NPs can selectively target cardiac tissues and efficiently deliver diverse bioactive molecules. EXPERT OPINION: CaP NPs represent a highly promising platform for cardiovascular therapy. Their safety and potential for noninvasive inhalation administration could enable precise, effective, and patient-friendly treatments. Future research, including comparative studies with other nanocarriers, will help to validate their therapeutic potential. Continued development of CaP NP-based strategies may transform CVD management by enabling molecular-level interventions that improve clinical outcomes, reduce systemic side effects, and allow rapid and convenient dosing.
Expert Opin Drug Deliv
· 2026 Jan · PMID 41267447
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INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer mortality, with poor outcomes driven by the tumor microenvironment (TME). Heterogeneous cancer-associated fibroblasts (CAFs) remodel the extracellular matr...INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer mortality, with poor outcomes driven by the tumor microenvironment (TME). Heterogeneous cancer-associated fibroblasts (CAFs) remodel the extracellular matrix (ECM), suppress immunity, and secrete cytokines that promote progression and resistance. As both barriers and therapeutic targets, CAFs are central to strategies aimed at overcoming treatment limitations in CRC. AREAS COVERED: We examine how CAF heterogeneity, with predominantly pro-tumorigenic but occasionally tumor-restraining functions, contributes to drug delivery resistance. This review highlights nanodrug delivery systems that integrate CAF targeting as a promising strategy to enhance therapeutic efficacy. Approaches include passive and active targeting of ECM degradation to improve drug penetration, advanced carriers for CAF reprogramming, CAF markers, and multifunctional platforms combining chemo- and immunotherapy. Literature was identified through PubMed, Web of Science, Scopus, and ClinicalTrials.gov searches up to September 2025, focusing on CAF biology, nanodrug delivery, and CRC translation. EXPERT OPINION: CAF-targeted nanodrug delivery offers a transformative opportunity to address long-standing barriers in CRC therapy. Future advances will depend on the integration of multi-omics CAF subtyping, rational combination regimens, and clinically scalable nanocarriers to translate these strategies into a lasting clinical benefit.
Expert Opin Drug Deliv
· 2026 Jan · PMID 41265890
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INTRODUCTION: Plant-derived extracellular vesicles (PDEVs) have emerged as natural nanocarriers with promising applications in drug delivery and precision medicine. Secreted by plant cells, PDEVs facilitate intercellular...INTRODUCTION: Plant-derived extracellular vesicles (PDEVs) have emerged as natural nanocarriers with promising applications in drug delivery and precision medicine. Secreted by plant cells, PDEVs facilitate intercellular communication by transporting metabolites. Unlike conventional liposomes and mammalian-derived EVs, PDEVs demonstrate excellent biocompatibility, stability, and the ability to cross biological barriers without inducing inflammatory or cytotoxic effects. Their capacity to encapsulate both hydrophilic and hydrophobic therapeutic agents highlight their versatility as targeted delivery platforms. AREAS COVERED: This review summarizes PDEV biogenesis in comparison with mammalian-derived EVs and emphasizes characterization techniques and the role of lipid components in drug delivery efficacy. Drug loading strategies are critically examined with respect to their efficiency, advantages, and limitations. Advances in engineering, including surface modification and hybrid vesicle formation, are discussed to enhance targeting precision, circulation stability, and controlled drug release. Therapeutic potential and synergetic application in disease prevention and management are evaluated, alongside key considerations such as storage stability, current limitations, and opportunities for clinical translation. EXPERT OPINION: PDEVs represents a promising platform for drug delivery and precision medicine. Although large-scale production, standardization and long-term stability remain challenges, recent innovations in loading strategies and engineering approaches demonstrate significant potential to overcome these barriers and accelerate clinical translation.
Li Z, Jin W, Zhu M
… +8 more, Feng Y, Fan G, Zhao J, Lee JS, Li X, Li Y, Lu Y, Dong Z
Expert Opin Drug Deliv
· 2026 Jan · PMID 41261875
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INTRODUCTION: Plant-derived extracellular vesicles (PEVs) have shown significant promise as a novel oral delivery system for nucleotide-based drugs. The successful oral delivery of nucleotide drugs using PEVs paves the w...INTRODUCTION: Plant-derived extracellular vesicles (PEVs) have shown significant promise as a novel oral delivery system for nucleotide-based drugs. The successful oral delivery of nucleotide drugs using PEVs paves the way for developing innovative nucleotide delivery systems in terms of inflammatory bowel disease, cancer and metabolic diseases treatment. By utilizing surface and other engineering modifications, PEVs can circumvent the challenges of oral administration posed by the gastrointestinal barrier and enzymatic degradation. AREAS COVERED: This review covers PEVs as oral nucleotide carriers, focusing on their anti-inflammatory, anticancer, and metabolic disease applications. It includes engineered modification methods (ligand, polymer modification, fusion) and nucleotide delivery application. This review searched for keywords using literature retrieval websites such as PubMed, Embase, and Google Scholar. EXPERT OPINION: This review introduces recent advancements of PEV-based technologies focused on ingestible nucleotide delivery, not only contributing valuable theoretical insights but also offering practical guidance for future precision medicine and drug development by PEVs. However, the current existence of regulatory ambiguity and low production efficiency has hindered the clinical translation and large-scale application of PEV-based oral nucleotide delivery systems.
Expert Opin Drug Deliv
· 2026 Mar · PMID 41258700
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INTRODUCTION: Calcium carbonate particles are a very potent type of inorganic drug delivery carriers, which have attractive pH responsiveness, strong mechanical properties, and a relatively high loading capacity. Adding...INTRODUCTION: Calcium carbonate particles are a very potent type of inorganic drug delivery carriers, which have attractive pH responsiveness, strong mechanical properties, and a relatively high loading capacity. Adding organic constituents, like hydrogels, to calcium carbonate particles results in hybrid carriers, where the size, loading capacity, and release profiles can be controlled with higher precision. AREAS COVERED: This review summarizes recent progress in inorganic and hybrid CaCO₃ carriers, highlighting their potential for sustainable and targeted delivery including different methods of synthesis, analyzing loading and release as well as application of machine learning predictive capabilities to design the most desired polymorph: vaterite. Applications cover not only traditional and very extensive field of biomedicine but also delivery to plants in agriculture. EXPERT OPINION: Calcium carbonate, especially vaterite, offers a tunable, biocompatible platform for controlled and sustainable delivery. Hybrid CaCO₃-hydrogel systems address the limits of purely inorganic or organic carriers. Machine learning and explainable AI will accelerate synthesis and formulation optimization. Future progress depends on scalable, eco-friendly production and clear regulatory frameworks.
Expert Opin Drug Deliv
· 2026 Mar · PMID 41248261
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BACKGROUND: While generic inhalers are approved based on therapeutic equivalence to their reference listed drug (RLD) counterparts, design and labeling differences may unintentionally affect product usability and patient...BACKGROUND: While generic inhalers are approved based on therapeutic equivalence to their reference listed drug (RLD) counterparts, design and labeling differences may unintentionally affect product usability and patient adherence. Comparative use data for drug-device combination products such as inhalers is limited, leaving gaps in understanding how design variations influence use errors. RESEARCH DESIGN AND METHODS: This study systematically compared five RLD inhalers and eight US FDA-approved generic counterparts selected from the US FDA Orange Book. The data was analyzed using a structured framework to classify and compare physical characteristics, labeling elements, and instructional cues. RESULTS: Differences were identified across all five groups, including variations in device shape, mouthpiece design, dose counter placement, handling technique, and instruction. Group 1 showed the most differences. These differences may result in errors such as incorrect device handling, reduced drug deposition, or increased difficulty learning proper inhaler techniques. CONCLUSIONS: Findings revealed that design and labeling differences can introduce cognitive and physical product use challenges, potentially impacting proper inhaler use and patient adherence. While this study relied solely on publicly available materials, future work should incorporate user testing, digital human modeling, and assessments across patient populations with varying use characteristics.
Expert Opin Drug Deliv
· 2026 Jan · PMID 41236784
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INTRODUCTION: Despite high vaccination coverage, pertussis remains endemic, and epidemic cycles continue to occur every 3-5 years, illustrating the shortcomings of current vaccination strategies. Unlike current vaccines,...INTRODUCTION: Despite high vaccination coverage, pertussis remains endemic, and epidemic cycles continue to occur every 3-5 years, illustrating the shortcomings of current vaccination strategies. Unlike current vaccines, especially acellular pertussis vaccines, which prevent disease for short duration but do not prevent nasal colonization by the etiological agent , natural infection can induce durable immunity against disease and infection. Accordingly, live-attenuated nasal pertussis vaccine candidates have been developed to mimic the immunogenicity of natural infection without causing disease. AREAS COVERED: We summarize the current status of live-attenuated nasal pertussis vaccines based on a literature search with keywords 'pertussis vaccine,' 'live,' and 'attenuated.' These candidates were designed based on different strategies, including dependence on critical metabolites for bacterial growth, genetic attenuation of virulence, and modification of immunomodulatory properties of . EXPERT OPINION: Only vaccines based on genetic attenuation of virulence have reached clinical development thus far. The most advanced candidate is BPZE1, which has successfully completed six clinical studies, demonstrating safety, systemic and mucosal immunogenicity, and the ability to prevent or substantially reduce infection. If BPZE1 is eventually adopted for global use, it will likely be a major breakthrough in the ultimate control of pertussis, which has plagued humanity for centuries.
Giacobbo V, Gorgoglione F, Sevieri M
… +4 more, Bignami B, Tagliolini I, Corsi F, Mazzucchelli S
Expert Opin Drug Deliv
· 2026 Mar · PMID 41213168
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INTRODUCTION: Once regarded merely as an iron-storage protein, ferritin is now recognized as a dynamic nanoplatform with significant applications in nanomedicine. By leveraging its intrinsic tropism for tumor cells toget...INTRODUCTION: Once regarded merely as an iron-storage protein, ferritin is now recognized as a dynamic nanoplatform with significant applications in nanomedicine. By leveraging its intrinsic tropism for tumor cells together with its hollow cage structure, ferritin can be loaded with a variety of anticancer drugs. AREAS COVERED: Here, we provide a comprehensive overview of the advancements made in the use of heavy-chain ferritin (HFn)-based nanoparticles in oncology, with a specific focus on chemotherapy, phototherapy and imaging applications, while also broadening to include emerging developments in immunotherapy, in order to summarize the current state of the art. We identified relevant literature through PubMed and Scopus, focusing on studies published over the past five years. Our purpose goes beyond a basic description of applications, providing a critical discussion of their limitations within the oncology landscape and highlighting the current gap between research and clinical practice. EXPERT OPINION: While HFn nanocages show strong promise in vaccine development, their application in cancer treatment faces significant translational challenges. These include limited human data, variability in receptor expression, rapid clearance, and the need for more representative models and scalable manufacturing, though certain untargeted HFn-based systems as Gd-HFn and Dox-HFn appear closer to clinical readiness.
Expert Opin Drug Deliv
· 2026 Mar · PMID 41206781
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INTRODUCTION: Peptides play diverse roles in biological processes, including drug discovery, antibacterial activity, and protein-protein interactions, making peptide prediction a crucial field. The development of bioinfo...INTRODUCTION: Peptides play diverse roles in biological processes, including drug discovery, antibacterial activity, and protein-protein interactions, making peptide prediction a crucial field. The development of bioinformatics tools has significantly enhanced our ability to study and harness peptide potential. Among these, cell-penetrating peptides (CPP) are a unique class of polypeptides capable of crossing cell membranes, facilitating the intracellular delivery of therapeutic agents such as small molecules, peptides, proteins, and nucleic acids. This ability has expanded possibilities in drug delivery, gene therapy, and molecular imaging. However, identifying and designing effective CPP remains challenging. AREAS COVERED: In recent years, various computational tools and algorithms have been developed to predict the cell-penetration potential of peptides, aiding in the discovery of novel CPP and accelerating their applications. This review provides a comprehensive overview of bioinformatics tools including artificial intelligence (AI) for peptide prediction, with a particular focus on CPP. Systematic literature search was performed from PubMed, Embase, Scopus, and the Web of Science to cover published references related to the current topic from 2011 to October 2025. EXPERT OPINION: Understanding their functions and limitations will help researchers make informed decisions and effectively utilize peptide prediction in diverse scientific and clinical applications.
Mulet I Piera X, Del Campo-Montoya R, Cuadrado-Tejedor M
… +3 more, Garcia-Osta A, Garbayo E, Blanco-Prieto MJ
Expert Opin Drug Deliv
· 2026 Feb · PMID 41206776
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INTRODUCTION: Neurodegenerative diseases such as Parkinson's or Alzheimer's disease urgently require new therapeutic approaches. Despite significant efforts, no disease-modifying therapies targeting specific molecular pa...INTRODUCTION: Neurodegenerative diseases such as Parkinson's or Alzheimer's disease urgently require new therapeutic approaches. Despite significant efforts, no disease-modifying therapies targeting specific molecular pathways have demonstrated consistent clinical efficacy. This challenge has shifted attention toward drug delivery strategies that improve bioavailability, targeting, and patient accessibility. Intranasal delivery has emerged as a promising, non-invasive approach that bypasses the blood-brain barrier, and improves patient compliance. Lipid-based systems, especially following the success of COVID-19 vaccines, have gained attention as versatile platforms for delivering RNAs. Their ability to encapsulate diverse payloads and tunable composition makes them ideal candidates for targeting neurodegenerative disorders via the intranasal route. AREAS COVERED: This review discusses recent advances in intranasal delivery for the treatment of neurodegenerative disorders, emphasizing on lipid-based nanoparticles. It addresses formulation challenges such as stability, targeting efficiency, and compatibility with nasal physiology, and outlines key design parameters affecting brain delivery. Future directions are explored to advance formulation development and clinical translation. EXPERT OPINION: Intranasal lipid-based drug delivery represents a promising strategy to bypass the blood-brain barrier in neurogenerative disorder treatment. Although regulatory gaps and the absence of long-term safety evaluation, intranasal administration offers clear advantages for CNS targeting underscoring strong potential for future clinical translation.