Expert opinion on drug delivery最新文献

Introduction: In situ forming implants (ISFIs) are long-acting drug delivery systems that solidify at the injection site, creating a depot for sustained drug release from days to months. Compared with preformed implants, ISFIs offer unique advantages, including easier and more convenient administration and simpler manufacturing. Among the different types, solvent-based ISFIs are the most extensively studied and developed formulations.

Areas covered: This review analyses advances in solvent-based ISFIs at both preclinical and clinical levels, with emphasis on formulation strategies and therapeutic applications. A literature search was conducted using PubMed and WOS. EMA and FDA databases were also consulted.

Expert opinion: Solvent-based ISFIs represent an important strategy for achieving long-lasting effects with a single administration independent of patient compliance. Their main impact has been in mental and substance use disorders, but they are also useful for local effects. To date, one formulation has been approved for periodontitis, though applications in ocular diseases and osteoarthritis are anticipated. A key formulation challenge is to reduce the initial drug release. Most marketed formulations are based on PLGA/PLA dissolved in NMP. Recently, DMSO and PEGylated-based-ISFIs have been approved, which generally provide better drug release control and will likely lead to the development of new formulations.

Background: MR-107A-02 is a novel faster dissolving oral formulation of meloxicam to provide rapid absorption and faster onset of action in acute pain settings. This study compared the single-dose pharmacokinetics of MR-107A-02 tablets to reference meloxicam (Mobic®) tablets under fasting conditions.

Research design and methods: A single-dose, randomized, two-period crossover study was conducted at a single center in India. Healthy adult volunteers, aged 18-45 years, were randomized to receive a single, oral dose of 15 mg (1 × 15 mg) of MR-107A-02 or reference. Plasma samples were analyzed for meloxicam using LC-MS/MS. Pharmacokinetic parameters were derived using non-compartmental analysis, and 90% geometric confidence intervals for test/reference ratios were calculated. Safety was assessed through adverse event (AE) monitoring.

Results: Eighteen adult male volunteers were randomized and 16 completed the study. MR-107A-02 showed faster absorption, with a geometric mean C_max value of 2734.342 (ng/mL) compared to reference 1592.102 (ng/mL) and a significantly shorter median T_max (hour) (0.75 vs 4.00). There were no AEs, or serious AEs reported.

Conclusions: MR-107A-02 demonstrated more rapid absorption than reference, as evidenced by a higher C_max, and shorter T_max values. These findings highlight the potential utility of oral MR-107A-02's fast-release design in an acute pain setting.

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.

Introduction: Colorectal cancer remains one of the most prevalent and lethal malignancies worldwide, with treatment often hampered by poor drug bioavailability, systemic toxicity, and resistance to conventional therapies. Biomimetic nanocarriers have emerged as a promising strategy to overcome these limitations by combining nanotechnology with the biological functions of cell-derived membranes.

Areas covered: This review critically examines the design, fabrication, and application of biomimetic nanocarriers specifically for colorectal cancer. Focusing on various membrane coatings, including red blood cells, platelets, and cancer cells, and their role in enhancing drug delivery efficacy. It further explores the application of these nanocarriers in chemotherapy, immunotherapy, gene therapy, photothermal therapy, and cancer theranostics, while also discussing advances in targeting the unique tumor microenvironment of colorectal cancer.Literature was retrieved from PubMed, Scopus, Web of Science and Google Scholar databases covering publications from 2012 to May 2025.

Expert opinion: Despite encouraging preclinical results, the clinical translation of biomimetic nanocarriers faces challenges including scalability, membrane heterogeneity, immunogenicity, and regulatory hurdles. Furthermore, existing studies often overlook the unique features of the colorectal cancer tumor microenvironment. Future research should focus on precision nanomedicine tailored to colorectal cancer, addressing current limitations to enable safer, more effective, and targeted cancer management.

Background: In the present study, we fabricated a multifunctional hydrogel nanocomposite for wound healing applications.

Research design and methods: Computational simulations were employed to optimize gelatin and synthesize Ti3AlC2 (104) and clarify gelatin adsorption behavior on Ti3AlC2 (104). The experiments concentrated on the synthesis, characterization, and integration of Mxene into a gelatin hydrogel. The MTT assay, hemolysis assay, and antibacterial assay were performed to assess the in vitro biological activities of the hydrogels, and a full-thickness wound was induced on a rat for the animal experiments.

Results: The chosen composite exhibited a satisfactory docking score, with a binding energy of - 115.408 kcal mol^-1. The results showed that the synthesized MXenes had a zeta potential of +24.5 ± 3.2 mV and a hydrodynamic size of 2.091 ± 0.32 μm. The hydrogel that was made had a porous structure, was biodegradable, and could soak up much water. The biological test showed the hydrogel was biocompatible, hemocompatible, and antibacterial. The animal trials demonstrated that the MXene-loaded gelatin hydrogel expedited wound healing.

Conclusions: The fabricated gelatin hydrogel loaded with MXenes nanocomposite can be applied to contaminated wounds to eradicate the contamination and accelerate the healing process.

Introduction: Antimicrobial resistance (AMR) in bacterial infections is a critical global health threat, contributing significantly to increased morbidity and mortality. This challenge is further amplified by biofilms that act as a protective barrier around bacteria, limiting the effective action of antibiotics and host immune responses.

Areas covered: This review highlights the potential of nanoemulsion (NE) systems in delivering hydrophobic payloads, particularly essential oils (EOs), into biofilms, negatively charged extracellular polymeric substance (EPS) matrix. While essential oils exhibit strong antimicrobial properties, their effectiveness against biofilms is restricted due to poor bioavailability and limited biofilm penetration.

Expert opinion: NE systems employing natural, semisynthetic, and synthetic polymeric scaffolds offer an effective delivery method for EOs, enabling enhanced penetration into the negatively charged EPS matrix of biofilms. These therapeutics have significant potential for treating refractory biofilm-related AMR infections.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated significant clinical efficacy in recent years for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, their widespread application remains constrained by limitations such as low oral bioavailability and poor patient compliance due to frequent injections. This study developed a biphasic delivery system (Ex-NPs-gel) integrating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) thermosensitive hydrogel with nanoparticles (NPs) for sustained-release injectable formulations.

Methods: Exenatide-loaded nanoparticles (Ex-NPs) were prepared via the double emulsion solvent evaporation method and encapsulated into PLGA-PEG-PLGA hydrogel. The prepared NPs and hydrogel composite were subsequently evaluated for their physicochemical properties and in vitro/in vivo performance.

Results: In vitro studies demonstrated that Ex-NPs-gel achieved sustained exenatide release over 31 days with an initial burst release below 9% within the first 24 h. In T2DM rat models, a single administration induced fasting blood glucose stabilization for over 15 days and restored hepatic/pancreatic functions.

Conclusions: This system overcomes technical bottlenecks of conventional PLGA carriers and single-phase gels through modulation of release kinetics, offering a biocompatible and clinically translatable solution for long-acting polypeptide delivery.

Introduction: Nasal sprays offer a versatile, noninvasive delivery route for topical, systemic, immunological, and nose-to-brain therapies, yet effective targeting is limited by nasal anatomical complexity and physiological constraints.

Areas covered: The literature related suboptimal intranasal spray deposition to nasal valve constriction, convoluted nasal passages, mucociliary clearance, and vast geometrical variability. This review examined recent strategies that enhanced dosimetry realism and improved target delivery: (1) including mucus coating and nasal cycle effects, (2) optimizing delivery protocols such as the spray angle, head position, and dosing regimen, (3) engineering device features to improve targeting, and (4) tailoring formulation properties like the viscosity and surface tension to support liquid film translocation. Experimental findings highlighting protocol-driven improvements in spray targeting to the nasopharynx and olfactory region are also discussed.

Expert opinion: The effectiveness of nasal sprays hinges on their ability to deliver medication beyond the anterior nasal cavity to the intended target sites. Achieving this requires not only optimized spray dynamics and device design, but also the strategic use of liquid film translocation following initial deposition. Advances in physiologically realistic models and anatomically guided protocols will be key to unlocking the full therapeutic potential of nasal spray technologies.

Introduction: Systemic equilibrium, oral health, and digestion depend on the health of the salivary glands (SGs). SG disorders, such as Sjögren's syndrome, oral and maxillofacial cancer, and radiation-induced damage, are usually associated with xerostomia, which severely impacts the patient's quality of life. Current therapeutic modalities primarily provide symptomatic therapy without addressing the basic underlying tissue damage or promoting regeneration. Emerging pharmacological and stem cell treatments may restore SG function, but tailored delivery, effectiveness, and safety issues restrict their clinical application.

Areas covered: This review summarizes preclinical and clinical findings on systemic and localized stem cell and pharmaceutical drug administration. We discuss various SG conditions to match therapy methods to disease-specific demands and underline the necessity for accurate, efficient delivery systems to improve results and reduce adverse effects. We conclude with existing limits, future views, and prospective SG medicine regenerative therapy advancements.

Expert opinion: Advancements in drug and stem cell delivery systems for SGs offer the potential to move beyond symptomatic relief and instead regenerate damaged tissues. These approaches promise more targeted, cost-effective, and long-lasting therapies, though challenges like immune rejection, safety, and cost remain significant. Future research should focus on improving stem cell sources, delivery, and tracking, while integrating technologies such as gene editing, nanocarriers, and tissue engineering to enhance efficacy. Ultimately, treatment strategies are shifting toward regenerative solutions aimed at restoring SG function with fewer systemic side effects.