Expert opinion on drug delivery最新文献

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.

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.

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.

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.

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.

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.

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.

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.

Introduction: Advances in nanotechnology and nanomedicine increasingly focus on the rational design of smart nanocarriers capable of site-specific and stimulus-triggered drug release to improve therapeutic efficacy and reduce systemic toxicity. Among them, cyclodextrins (CDs), particularly cyclodextrin nanosponges (CDNSs), have emerged as safe, biodegradable, and versatile platforms for drug delivery due to favorable biocompatibility and structural adaptability.

Areas covered: CDNSs are three-dimensional, cross-linked polymeric networks formed through chemical reactions between cyclodextrins and suitable cross-linkers, generating porous architectures with high surface area and tunable physicochemical properties. These features enable efficient encapsulation of poorly water-soluble drugs and improvement of their solubility and bioavailability. Beyond conventional CD systems, stimulus-responsive CDNSs provide additional control by responding to internal or external triggers such as pH, temperature, light, and redox conditions. Particularly, glutathione-responsive CDNSs exploit intracellular redox gradients via disulfide bond cleavage, enabling selective drug release in cancerous and inflammatory tissues. Literature for this narrative review was identified through searches of PubMed, Web of Science, and Scopus, focusing on publications from 2000 to early 2025.

Expert opinion: This review highlights glutathione-responsive cyclodextrin nanosponges as an advanced evolution of CD-based carriers, emphasizing emerging structure - property - responsiveness relationships rather than exhaustive coverage. By discussing nanosponge architecture and cross-linking density.