ABSTRACT 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.

ABSTRACT 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 Bordetella pertussis, 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 Bordetella. 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 B. pertussis 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.

ABSTRACT Introduction Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to impaired ion transport by the CFTR protein and accumulation of thick, sticky mucus, resulting in chronic lung disease and other organ complications. Messenger ribonucleic acid (mRNA) therapies hold great potential for CF, as they can be used for both CFTR mRNA replacement and editing of the CFTR gene, which could mitigate the pathophysiological and clinical symptoms of CF. Areas covered We provide an overview of non-viral mRNA therapies for CF and their ongoing clinical trials. We begin with a discussion of the pathophysiological functions of CFTR and clinical symptoms of CF. We provide a summary of conventional treatments, modulator therapies, and potential gene therapies for CF. We discuss the pertinence of mRNA therapies for CF as well as the challenges associated with mRNA delivery. We conclude with an overview of non-viral vectors for mRNA delivery and a summary of clinical trials for CFTR mRNA therapies. Literature searches for this review were performed using databases (Google Scholar and PubMed). Expert opinion With continued innovation and overcoming of delivery challenges, mRNA therapies hold great potential for the treatment of people with CF, regardless of mutation.

ABSTRACT Introduction Pediatric intranasal (IN) drug delivery is a promising noninvasive way of administering medication, offering a significant improvement over parenteral and oral methods. However, its effectiveness is hindered by major technical challenges, primarily stemming from the wide anatomical variations among children and the difficulty in achieving consistent dosing. This expert opinion explores an integrated approach to overcome these obstacles. Areas covered This article summarizes the recent literature on technological strategies used to address challenges in pediatric drug delivery, focusing on studies published between January 2015 to December 2025, sourced from Google Scholar and PubMed. It discusses how advancements in formulation and device engineering are improving drug deposition and absorption. The article also highlights the relevance of regional deposition to two emerging applications: nose-to-brain drug delivery and intranasal vaccines, while also covering the challenges of the nasal mucus barrier and novel formulation strategies to overcome it. Expert Opinion The future of pediatric IN delivery lies in the coordinated advancement of multiple interdependent factors. By treating a child’s unique anatomy and physiology as key design parameters, researchers can integrate physical and computational models to simultaneously optimize formulations, devices, and delivery techniques. This multifactorial strategy will lead to highly reliable and personalized therapies.

ABSTRACT 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.

ABSTRACT Introduction Conventional drug delivery for cancer therapy often suffer from poor targeting efficiency, limited bioavailability, and severe off-target toxicity. Nanoparticle-based approaches have emerged as transformative alternatives, particularly when integrated with microfluidic technologies. In the context of liver cancer, microfluidic-assisted polymeric nanocarriers provide a highly controllable and reproducible route for improving drug delivery outcomes. Areas covered We cover recent developments in polymeric nanoparticle systems; their integration with microfluidic fabrication platforms for liver cancer therapy; the ability to encapsulate therapeutic agents, achieve controlled release, and facilitate passive and active tumor targeting through physicochemical modulation and ligand functionalization; microfluidic-assisted synthesis, which enables fine-tuned control over particle size, surface chemistry, and payload distribution with minimal batch-to-batch variation; PEGylated PLGA, cyclodextrin-based, and stimuli-responsive polymeric nanocarriers, highlighting their potential in overcoming biological barriers and enhancing therapeutic index. Expert opinion Microfluidic-assisted nanoparticle fabrication represents a paradigm shift in the design and clinical translation of targeted therapies for liver cancer. By allowing real-time control over nanoparticle synthesis and enabling combination delivery strategies, this approach holds great promise for personalized and precision oncology. Continued integration of microfluidic engineering with biomaterial science and clinical insights is expected to accelerate the realization of safe, reproducible, and patient-tailored nanotherapeutics for hepatocellular carcinoma.

ABSTRACT Introduction Conventional drug delivery systems in cancer therapy face limitations such as poor targeting and adverse side effects. Nanoparticle-based approaches, particularly when integrated with microfluidic technology, have emerged as promising strategies to improve therapeutic precision and outcomes, especially in liver cancer treatment. Areas covered This review discusses recent progress in the use of nanoparticles and polymers for targeted drug delivery, highlighting their ability to encapsulate therapeutic agents and release them at specific sites. The role of microfluidic platforms in drug loading is emphasized, as they enable precise manipulation at micro- and nanoscale levels with minimal sample loss. Literature examining the use of polymer-based nanocarriers, microfluidic-assisted drug encapsulation, and their applications in overcoming tumor growth and liver cancer therapy is analyzed. The article also explores the advantages of microfluidics as a tool for fabricating complex nanosystems for controlled and efficient delivery. Expert opinion Microfluidic-assisted nanoparticle delivery represents a highly promising approach for advancing liver cancer treatment. With its potential to support combination therapies and enable intricate, customizable nanosystems, this platform is likely to shape the future of targeted cancer therapeutics.

ABSTRACT 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.

ABSTRACT Introduction Conventional treatment for Denture Stomatitis (DS) uses antifungals, but microbial resistance and adverse effects from prolonged use have led to the search for alternatives. In this context, Curcumin shows promise due to its antimicrobial and anti-inflammatory properties. This is to systematically review and evaluate the efficacy of topical curcumin in different drug delivery systems for treating DS, compared to other therapies. Methods Two independent reviewers conducted a literature search between August 2024 and March 2025 across seven databases: PubMed, BVS/Medline, EMBASE, SciELO, CAPES Journals, Google Scholar, and BDTD. Clinical trials with no language or publication date restrictions were included. Risk of bias was assessed using RoB 2, and evidence quality was evaluated via the GRADE system. Results The search identified 20,675 articles. After applying eligibility criteria, five randomized clinical trials involving 207 participants were included. Drug delivery systems used were mouthwash, ointment, and photodynamic therapy with curcumin solution. All studies reported a reduction in C. albicans colony count. However, the quality of evidence (GRADE) is moderate, with inconsistencies and risk of bias affecting outcomes. Conclusion Topical use of curcumin can reduce the number of Candida albicans CFU/clinical signs in patients with denture stomatitis, but the quality of the evidence is moderate. Protocol registration CRD42024549944.