Expert Opin Drug Deliv
· 2026 Mar · PMID 41204741
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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 hindere...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.
Gill NA, Fung V, VanKeulen-Miller R
… +2 more, Narasipura EA, Fenton OS
Expert Opin Drug Deliv
· 2026 Mar · PMID 41202203
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INTRODUCTION: Cystic fibrosis (CF) is a genetic disease caused by mutations in the (CFTR) gene, leading to impaired ion transport by the CFTR protein and accumulation of thick, sticky mucus, resulting in chronic lung di...INTRODUCTION: Cystic fibrosis (CF) is a genetic disease caused by mutations in the (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 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.
Ebrahimiverkiani A, Ebrahimi Varkiani M, Jadid Tavaf M
… +2 more, Naghib SM, Rabiee N
Expert Opin Drug Deliv
· 2026 Mar · PMID 41201582
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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 technolog...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.
Ebrahimiverkiani A, Ebrahimi Varkiani M, Jadid Tavaf M
… +2 more, Naghib SM, Rabiee N
Expert Opin Drug Deliv
· 2026 Mar · PMID 41201532
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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 transformati...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.
Li X, Wang X, Tong F
… +3 more, Li H, Gao H, Liu T
Expert Opin Drug Deliv
· 2026 Feb · PMID 41178011
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INTRODUCTION: The nose-to-brain route is a promising noninvasive strategy to circumvent the blood-brain barrier (BBB) and directly target the central nervous system (CNS), addressing the pivotal challenge of poor drug de...INTRODUCTION: The nose-to-brain route is a promising noninvasive strategy to circumvent the blood-brain barrier (BBB) and directly target the central nervous system (CNS), addressing the pivotal challenge of poor drug delivery in neurology. This review provides a strategic overview of the biological barriers and advanced nano-strategies, offering a roadmap for future research and clinical translation. AREAS COVERED: This review explores the nose-to-brain route, from its anatomical basis and physiological barriers (mucus, epithelium, brain distribution), to interventional nanocarriers. These include systems with mucoadhesive/penetrative coatings, junction modulators, and targeted, environmentally responsive designs. The literature search was conducted utilizing databases such as PubMed and Web of Science, covering records from their inception up to August 2025, using a combination of keywords and MeSH terms including 'nose-to-brain delivery,' 'intranasal administration,' 'nanoparticles,' and 'neurological disorders.' EXPERT OPINION: Despite the remarkable preclinical progress in enhancing brain drug concentrations, the clinical translation of nose-to-brain nanoplatforms remains hindered by challenges related to long-term safety, inter-individual variability, and scalable manufacturing; future success hinges on the development of intelligent, responsive systems and interdisciplinary collaboration to achieve personalized and effective neurological therapies.
Guo J, Sun Y, Zhang D
… +4 more, Yan J, Ji S, Chen W, Gu X
Expert Opin Drug Deliv
· 2026 Mar · PMID 41178001
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INTRODUCTION: With the rapid expansion of the biopharmaceutical industry, particularly in chronic disease treatment and immunotherapies, self-injection has emerged as a preferred method for patient-administered therapies...INTRODUCTION: With the rapid expansion of the biopharmaceutical industry, particularly in chronic disease treatment and immunotherapies, self-injection has emerged as a preferred method for patient-administered therapies. AREAS COVERED: Prefilled syringe (PFS)-based autoinjectors have become the most widely adopted self-injection devices due to their convenience, efficiency, and acceptance by patients, caregivers, and healthcare providers. Despite the growing interest and increasing FDA approvals for autoinjector products, comprehensive reviews focusing specifically on disposable PFS-based autoinjectors remain limited. This review addresses that gap by systematically analyzing based on data retrieved from the U.S. Food and Drug Administration's official website, including FDA-approved New Drug Applications (NDAs) and Biologics License Applications (BLAs) since 1980. EXPERT OPINION: Furthermore, the technical challenges in incorporating injectable formulations into spring-driven autoinjector systems are discussed. This review aims to facilitate the development of safer, more efficient autoinjector platforms that enhance user experience and treatment adherence.
Expert Opin Drug Deliv
· 2026 Feb · PMID 41144949
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INTRODUCTION: Controlled drug delivery systems are transforming immunomodulation by providing targeted, localized control of immune activity in chronic diseases, including autoimmunity, infection, and cancer. Unlike conv...INTRODUCTION: Controlled drug delivery systems are transforming immunomodulation by providing targeted, localized control of immune activity in chronic diseases, including autoimmunity, infection, and cancer. Unlike conventional systemic therapies that cause systemic toxicity and relapse, these platforms deliver fine-tuned immune responses through sustained, localized release to enhance efficacy while minimizing adverse effects. AREAS COVERED: This review explores current strategies using nanoparticles, microparticles, hydrogels, and implant technologies to achieve targeted immune suppression, activation, or tolerance across diverse applications. Controlled drug delivery systems enable precise spatial and temporal dosing to protect transplanted tissues, induce antigen-specific tolerance in autoimmune disorders, and amplify immune activation in vaccines and cancer immunotherapy. We also discuss emerging frontiers in precision immunoengineering, such as leveraging CRISPR technologies. EXPERT OPINION: While translational and regulatory hurdles remain, controlled delivery platforms provide a versatile framework for patient-specific immune modulation. In our Expert Opinion, we highlight their potential to reshape clinical immunotherapy by improving long-term outcomes and enabling personalized immunomodulation, while identifying translational barriers and emerging directions.
Hoang TPN, Timmins P, Smith AM
… +2 more, Conway BR, Ghori MU
Expert Opin Drug Deliv
· 2026 Feb · PMID 41143521
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INTRODUCTION: Natural bioflavonoids, particularly hesperidin from citrus fruits, have attracted attention due to their potent antioxidant, anti-inflammatory, anticancer and neuroprotective properties. However, the clinic...INTRODUCTION: Natural bioflavonoids, particularly hesperidin from citrus fruits, have attracted attention due to their potent antioxidant, anti-inflammatory, anticancer and neuroprotective properties. However, the clinical application of hesperidin is limited by its poor solubility, low bioavailability, and stability issues. METHODS: Following PRISMA guidelines, we searched PubMed, MEDLINE, Scopus, and Google Scholar from inception to 10 January 2025 using terms combining 'hesperidin' with 'bioavailability,' 'solubility,' 'absorption,' and 'formulation.' Two reviewers independently screened records against predefined inclusion criteria (original, formulation-focused studies reporting biopharmaceutical or biological outcomes), resolved disagreements through discussion or third-reviewer adjudication, extracted data using a standard template, and assessed the risk of bias across six domains. RESULTS: From 1,625 records, 69 studies met eligibility. Platforms spanned inclusion complexes, solid dispersions, self-microemulsifying drug delivery systems (SMEDDS), microparticles, gels/microemulsions, and diverse nanoformulations (polymeric, lipidic, metallic, exosomal). Most approaches increased dissolution and/or exposure; lipidic and polymeric nanosystems delivered the largest, most consistent improvements, with early clinical signals in vascular, metabolic and oncological indications. CONCLUSIONS: Formulation advances can significantly mitigate hesperidin's biopharmaceutical liabilities, with lipid-based systems, polymeric nanoparticles, and phytosomes emerging as leading strategies. Translation will benefit from stability and immunotoxicity packages, quality-by-design manufacturing, and well-designed, adequately powered clinical trials using harmonised pharmacokinetic and clinical endpoints. INPLASY REGISTRATION: INPLASY202550096.
Expert Opin Drug Deliv
· 2026 Feb · PMID 41139849
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INTRODUCTION: One of the reasons for the decreasing effectiveness of modern antimicrobial chemotherapy and the increasing resistance of pathogenic microorganisms to drugs is a hampered access of active agents to intracel...INTRODUCTION: One of the reasons for the decreasing effectiveness of modern antimicrobial chemotherapy and the increasing resistance of pathogenic microorganisms to drugs is a hampered access of active agents to intracellular targets, due to the problems with crossing the biological membrane barriers. AREAS COVERED: This article discusses the possibilities and methods of using oligopeptides that penetrate cell membranes by simple diffusion, endocytosis, or using active transport systems, as molecular carriers for the construction of antimicrobial conjugates, following the Trojan Horse strategy. The basis for the discussion and conclusions is a critical review of the literature from 1970 to 2025, searched in Web of Science, PubMed, and Scopus, with a strong emphasis on examples from the last decade. EXPERT OPINION: Application of short peptides transported by microbial oligopeptide transport systems, cell penetrating peptides, and antimicrobial peptides as molecular carriers may give rise to novel antimicrobial conjugates, able to overcome microbial resistance, as well as to enhancement of antimicrobial potential and broadening of antimicrobial spectrum of existing drugs, especially against intracellular microbial pathogens.
Qamar Z, Khan SA, Kumari P
… +6 more, Khan M, Krishna PVVS, Dang S, Baboota S, Ali A, Ali J
Expert Opin Drug Deliv
· 2026 Feb · PMID 41123927
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INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a bleak prognosis, complicated by factors such as the blood-brain barrier (BBB), the tumor's heterogeneity, and the systemic toxicity as...INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a bleak prognosis, complicated by factors such as the blood-brain barrier (BBB), the tumor's heterogeneity, and the systemic toxicity associated with standard therapies. Utilizing receptor-mediated delivery through nasal routes with polymeric nanocarriers provides a noninvasive approach to enhance brain targeting, improve therapeutic outcomes, and increase safety. AREA COVERED: This review focuses on polymeric nanocarriers, including nanoparticles, nanocapsules, dendrimers, and micelles, for use in combination therapy for GBM. It emphasizes targeting overexpressed receptors, advanced carrier designs that enable controlled or responsive release, and multifunctional systems with theranostic capabilities. Additionally, it highlights immunomodulatory and personalized strategies, underscoring their importance for clinical translation. EXPERT OPINION: Polymeric nanocarriers designed for receptor-mediated delivery from the nose to the brain offer a revolutionary approach for combination therapy in GBM, enhancing drug absorption, specificity, and therapeutic effectiveness. Although promising advancements have been made in preclinical studies, their translation to clinical settings is hindered by physiological barriers in the nose, complex formulations, and challenges related to scalability. Moving forward will necessitate refined nanocarrier design, accurate receptor targeting, and thorough clinical testing to confirm these systems as advanced treatment platforms for GBM.
Expert Opin Drug Deliv
· 2026 Feb · PMID 41121460
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INTRODUCTION: The nasal route is attracting increasing interest for delivering therapeutics and vaccines. The application of novel technologies, such as microfluidic organ-on-chips for relevant nasal drug tests, is high...INTRODUCTION: The nasal route is attracting increasing interest for delivering therapeutics and vaccines. The application of novel technologies, such as microfluidic organ-on-chips for relevant nasal drug tests, is highlighted in the literature. AREAS COVERED: This report highlights the advantages of using microfluidics for studying aerosols, sheds light on the potential challenges and suggests solutions for future research in nasal aerosols studies. This report covers research available at peer-reviewed journal article databases, including PubMed and Scopus from the past 10 years up to September 2025. EXPERT OPINION: Accurate modeling of the nasal airway microenvironment, including airflow and the associated mechanical stresses, is necessary to replicate the realistic interaction between aerosol particles and their surrounding geometries as they traverse complex respiratory pathways through the nose. Novel measures and techniques to complement organ-on-chip devices will be critical to replicating the transport and deposition of aerosols in realistic nasal airways. Future research may focus on the development of more powerful tools that enable high-throughput examinations of nasal aerosols, delivering simultaneous insights into particle behavior and tissue responses.
Qamar Z, Khan SA, Kumari P
… +6 more, Khan M, Krishna PVVS, Dang S, Baboota S, Ali A, Ali J
Expert Opin Drug Deliv
· 2026 Feb · PMID 41116650
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INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive tumor with poor survival rates. Current treatment strategies are hindered by blood - brain barrier (BBB), which limits the delivery of medication, and by...INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive tumor with poor survival rates. Current treatment strategies are hindered by blood - brain barrier (BBB), which limits the delivery of medication, and by systemic toxicity and insufficient drug levels at the tumor site. A promising new approach, nose-to-brain delivery, offers noninvasive way to bypass the BBB through the olfactory and trigeminal pathways, allowing for direct brain targeting. One promising method, receptor-mediated transport, utilizes receptors found on nasal epithelial cells and glioblastoma cells to enhance drug uptake at the tumor site. However, this approach faces challenges, including difficulties with mucociliary clearance, dosing issues, and variations in medication response among patients. AREA COVERED: This review offers an overview of receptor-mediated nose-to-brain delivery strategies for GBM. It focuses on nasal pathways, transport mechanisms, and key receptors, including transferrin, insulin, folate, and integrins. The review highlights that targeting these receptors can enhance delivery efficiency, increase brain penetration, and facilitate the co-delivery of drugs to address tumor heterogeneity and resistance. EXPERT OPINION: Receptor-mediated intranasal delivery offers a promising strategy for GBM therapy. Advancing this approach will require precise receptor targeting and robust clinical validation to ensure effective translation from bench to bedside.
Expert Opin Drug Deliv
· 2026 Feb · PMID 41115177
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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...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.
Expert Opin Drug Deliv
· 2025 Dec · PMID 41103167
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INTRODUCTION: Intranasal drug delivery offers a noninvasive, rapid, and metabolically advantageous route for local and systemic therapies. However, achieving targeted and efficient delivery remains a significant challeng...INTRODUCTION: Intranasal drug delivery offers a noninvasive, rapid, and metabolically advantageous route for local and systemic therapies. However, achieving targeted and efficient delivery remains a significant challenge due to the nasal cavity's complex anatomy, protective airflow structures, and physiological variability. Traditional focus on formulation chemistry overlooks the critical role of fluid and particle dynamics in determining drug fate. AREAS COVERED: This review synthesizes decades of research on nasal drug delivery with a focus on biophysical and aerodynamic considerations. The literature review covered clinical studies, CFD investigations, and emerging device innovations. The article progresses from clinical targets and barriers (anatomical and human factors) to particle-fluid dynamics governing deposition, leading into advances in experimental and computational models to understand how to overcome these barriers, culminating in translational insights and future directions. EXPERT OPINION: Patient-specific, GPU-accelerated CFD simulations, increasingly refined by AI, will enable predictive deposition mapping and integration with PBPK models. This supports in silico trials and personalized device optimization, yet clinical translation is limited by validation gaps, regulatory conservatism, and manufacturing complexities. Future integration of real-time imaging, AI surrogates, and smart delivery systems may shift nasal drug delivery toward per-nostril precision medicine and virtual-cohort-based regulatory acceptance.
Das S, Kumar M, Mukherjee S
… +3 more, Shafi S, Singh AK, Mishra MK
Expert Opin Drug Deliv
· 2026 Jan · PMID 41088787
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INTRODUCTION: Bi-gels are a novel drug delivery system that enhances the regulated and targeted release of anticancer therapies by combining hydrogels and organogels. These dual-phase systems, including a hydrophilic pol...INTRODUCTION: Bi-gels are a novel drug delivery system that enhances the regulated and targeted release of anticancer therapies by combining hydrogels and organogels. These dual-phase systems, including a hydrophilic polymer network (hydrogel) and a lipophilic polymer network (organogel), enable the simultaneous administration of hydrophilic and lipophilic pharmaceuticals. In bi-gels, the aqueous and organic phases provide complementary functions. AREAS COVERED: This study examines the principles of bi-gels, encompassing their definition, composition, gelation processes, and preparation techniques. It emphasizes the design and formulation techniques for cancer treatment, concentrating on polymeric materials, phase roles, and encapsulation parameters. The discussion encompasses targeting strategies including passive mechanisms (EPR effect), active mechanisms (ligand-receptor interactions), and response to the tumor microenvironment. Applications in oncology, namely bi-gel systems treating cutaneous malignancies, are highlighted. The review combines formulation science with therapeutic targeting to introduce bi-gels as potential platforms for regulated drug delivery and improved anticancer effectiveness. EXPERT OPINION: Bi-gels are sophisticated dual-phase drug carriers created by several gelation processes. They facilitate efficient encapsulation, phase-controlled delivery, and tumor-specific targeting via ligand interactions and microenvironment sensitivity, presenting promising applications in cancer therapy with improved precision and bioavailability.