Expert opinion on drug delivery最新文献

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.

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Background: The MedRing is an innovative, flexible vaginal ring that, unlike other rings, allows personalized drug administration and monitoring. This study evaluated its user acceptability and ease of use.

Research design and methods: This was an exploratory, prospective, open-label, interventional, multicenter study. Twenty-one women (25 - 75 years) used the dummy/placebo MedRing for three weeks, with insertions/removals on day 1 and after weeks 1 and 3. Participants scored design, ease of self-insertion/removal, wearing comfort, and potential future use. They also kept a daily diary, rating comfort on a 10-point scale (1 = intolerable, 10 = no problem). In addition, physicians rated ease of use and complications on a 5-point scale (1 = no problem; 5 = problematic). Safety evaluations included vaginal examinations and adverse event (AE) monitoring. Data were analyzed descriptively.

Results: After three weeks, the median (min-max) overall acceptance score was 9.5 (5 - 10); insertion and removal scored 10 (8-10) and 9 (3-10), respectively. Median comfort scores ranged 8-10. The physician's ease-of-insertion/removal median score was 1 (1 - 5). Two participants discontinued due to AEs: inability to remove the ring and vaginal irritation.

Conclusion: The MedRing demonstrated high user acceptability and ease of use, supporting its use as a personalized, self-controlled treatment device across a wide age range.

Introduction: Prostate cancer (PC) treatment is limited by resistance mechanisms and cumulative toxicities, necessitating novel therapeutic strategies. While curcumin and piperine exhibit potent anticancer properties, their clinical utility is severely compromised by poor bioavailability and rapid metabolism.

Areas covered: This review critically analyzes the preclinical and clinical landscape of curcumin and piperine nanoformulations (CPN) for the treatment of PC. We utilized PubMed and Scopus (2000-2025) to evaluate molecular mechanisms, focusing on CYP17A1 inhibition, PI3K/Akt/mTOR signaling, and ferroptosis. The report examines the physicochemical properties of nanocarriers, including PLGA and liposomes, and addresses translational barriers such as the heterogeneity of the Enhanced Permeability and Retention (EPR) effect, stromal density, and risks associated with piperine-mediated drug - drug interactions.

Expert opinion: While nano-encapsulation enhances the therapeutic index of curcumin, clinical translation remains stalled by a reliance on passive targeting and insufficient manufacturing scalability. Future success depends on shifting from 'beaker' synthesis to microfluidic production (Quality by Design) and adopting active targeting (e.g. PSMA-directed delivery) to penetrate the prostate stroma. Without these strategic pivots and biomarker-driven trials, CPNs risk remaining an academic curiosity rather than evolving into a viable clinical intervention.

Introduction: Drug-loaded nanofibrous systems represent a breakthrough in drug delivery, overcoming limitations of conventional formulations. They demonstrate controlled morphology and flexibility across multiple administration routes, with versatility delivering small-molecule and biological drugs, and supporting diverse technological implementations. These platforms address unmet clinical needs in dissolution enhancement, drug stabilization, targeted delivery, thus enhancing bioavailability.

Areas covered: The expert review critically evaluates formulation design innovations, scalable manufacturing technologies, and application-specific challenges across buccal, nasal, ophthalmic, transdermal, implantable and vaginal nanofibrous systems. It covers the regulatory framework and clinical status while addressing the gap between research and industrial implementation. It emphasizes the critical limitations, drawbacks, and manufacturing barriers that have prevented widespread clinical adoption, alongside strategies to overcome obstacles.

Expert opinion: Nanofibrous drug delivery systems offer advantages in dissolution enhancement, biological protection, and patient-tailored administration. However, industrial implementation and regulatory acceptance remain constrained by scalable manufacturing, cost-effectiveness and regulatory harmonization. Despite promising preclinical results, no pharmaceutical drug-loaded nanofiber product has yet achieved FDA or EMA approval.Clinical translation requires process innovation, quality assurance, and demonstrated superiority, supported by artificial intelligence, digital sensors and 3D printing technologies. Over the next five years, nanofiber-based technologies are anticipated to drive innovation in patient-centered therapies.