Expert opinion on drug delivery最新文献

Introduction: Oral dopaminergic treatment is the cornerstone of Parkinson's disease (PD) management. However, progressive shortening of oral levodopa's effect, along with the limited efficacy of enzyme inhibitors and dopamine agonists, does not allow to adequately control motor and non-motor complications characterizing advanced PD. At this stage, device-aided therapies (DATs), including infusion treatments, are warranted to guarantee an adequate quality of life.

Areas covered: We review current and upcoming infusion therapies for PD, with a particular focus on their efficacy and safety data. Moreover, we provide an overview of current knowledge and open issues on patient selection and specific DAT choice.

Expert opinion: Recent EAN/MDS-ES guidelines suggest infusion therapies for advanced PD, yet several challenges remain, including limited access, delayed referrals, and patients' hesitancy. The '5-2-1' criteria and tools like MANAGE-PD aid early identification of eligible candidates, but treatment decisions often do not account for patients' preferences. Current trends favor early DATs implementation, as soon as motor fluctuations appear and before the disability onset. Emerging infusion therapies (e.g. foslevodopa-foscarbidopa) will boost this tendency. Enhancing DATs accessibility and inclusivity in clinical trials are key priorities. Finally, regenerative therapies including putaminal infusion of neurotrophic factors and dopaminergic neuron precursors may transform advanced PD care.

Introduction: Hollow microneedles (HMNs) offer a minimally invasive and highly efficient method for transdermal drug administration, overcoming the limitations of traditional delivery systems.

Areas covered: This review focuses on recent advancements in 3D-printed HMNs, highlighting their transformative potential in drug delivery applications. The integration of cutting-edge 3D printing technologies, such as stereolithography (SLA), digital light processing (DLP), and two-photon polymerization (2PP), has enabled the fabrication of complex, precise, and customizable microneedles (MNs). These innovations facilitate patient-specific applications, enhance drug bioavailability, and provide unparalleled control over dosage and delivery. Advances in biocompatible and biodegradable materials have further improved the safety and functionality of HMNs. Applications range from insulin delivery to biomarker sensing and theranostic systems, showcasing their versatility.

Expert opinion: 3D-printed HMNs are set to play an important role in improving personalized medicine and precision healthcare. By addressing fabrication and design issues, and using new materials, these devices are expected to change drug delivery systems and help develop new therapeutic and diagnostic platforms.

Introduction: Inflammatory bowel diseases (IBD) are chronic gastrointestinal disorders with rising global incidence. Current therapies often suffer from systemic side effects, limited efficacy, and poor patient compliance, particularly with injectable formulations. These limitations underscore the need for innovative oral delivery strategies capable of targeted action in the inflamed intestine.

Areas covered: This review provides an in-depth overview of zein nanoparticles as drug delivery systems for IBD. The discussion covers recent studies on zein nanoparticles containing anti-inflammatory compounds, focusing on their behavior in gastrointestinal environment, their ability to overcome biological barriers, and their potential to enhance therapeutic outcomes. Special focus is placed on advanced multistage systems designed to extend mucosal retention time and enhance drug accumulation at inflamed sites.

Expert opinion: Zein nanoparticles offer a promising and multifunctional platform for IBD therapy. Beyond their role as carriers, their intrinsic antioxidant properties and ability to stimulate endogenous GLP-1 secretion suggest a dual therapeutic action combining drug delivery with mucosal healing and immune modulation. Clinical translation requires overcoming key barriers, including limited mucus penetration, interpatient variability, and challenges in large-scale production. Continued technological advancements may establish zein nanoparticles as a viable carrier for targeted, effective, and patient-compliant oral therapies in IBD.

Introduction: Nanocrystals (NCs) combined with microneedles (MNs) represent an emerging drug delivery platform with significant potential to overcome challenges in the administration of poorly-water soluble drugs. This next generation delivery approach increases the surface area and dissolution rate of drugs via the production of NCs, overcoming the skin barrier in a minimally invasive manner, afforded by the MN technology.

Areas covered: This focused review summarizes the research from the past eight years on the development of NC-loaded MN systems. It discusses the formulation strategies, characterization, and therapeutic benefits reported in the literature, highlighting controlled dissolution and sustained release capabilities. The review also addresses critical challenges related to clinical translation, such as validation of therapeutic efficacy and broadening clinical applications.

Expert opinion: NC - MN systems have shown promise in self-administered and long-acting therapies. Yet, stability issues, manufacturing reproducibility, and regulatory uncertainty still remain barriers to translation. Progress in scalable manufacturing and regulatory engagement is encouraging, but robust in vivo data and standardized characterization are needed. Continued interdisciplinary work and collaboration across academia, industry, and regulatory agencies will be vital to realize the clinical potential of this platform.

Introduction: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with long-established clinical relevance in cancer therapeutics and diagnostics. Their elevated activity in the tumor microenvironment is associated with key pathological processes such as metastasis, angiogenesis, and cancer cell invasion.

Areas covered: This review highlights recent developments in the design of MMP-responsive drug delivery systems that leverage the aberrant proteolytic activity of MMPs for targeted and spatiotemporally controlled drug delivery. Key strategies include the use of MMP-cleavable hydrogels, responsive nanoparticles, and various prodrug designs. While MMPs have historically been pursued as therapeutic targets, their physiological role has complicated this approach and led to little success. Instead, recent efforts have reframed MMP activity as a trigger for site-specific drug activation, offering improved precision in cancer treatment. The review also discusses current challenges and the translational progress of these delivery systems.

Expert opinion: Exploiting MMP dysregulation in the tumor environment represents a logical next step in cancer treatment. Drug delivery systems that achieve MMP-responsive activation while reducing off-target effects and enhancing drug retention, circulation, or uptake are key to practical translation. Clinical realization of MMP-responsive delivery systems requires further refinement in protease selectivity, stability, and integration of other stimuli-responsive designs.

Introduction: Osteoarthritis (OA) is a prevalent degenerative joint disease, affecting millions worldwide and imposing a huge medical burden. Traditional OA treatments focused on symptom relief rather than delaying disease progression. Due to the anatomical structure and physiological characteristics of the joint, systemic and intra-articular drug administration face limitations. Recently, cell membrane-coated nanoparticles have emerged as a promising strategy for OA treatment. By leveraging the intrinsic characteristics of cell membranes, these engineered nanoparticles enhance drug retention, immune evasion, and targeted efficacy.

Areas covered: This review summarizes the current research on different cell membrane-coated nanoparticles used in OA treatment, presenting the development of cell membrane-coated nanoparticles drug delivery system to target joint.

Expert opinion: Cell membrane-coated nanoparticles, which improve the delivery performance and shortcomings of traditional nanoparticles, provide a novel insight into OA drug delivery strategy. They offer tremendous potential in addressing the challenges associated with traditional drug delivery. However, it is still important to assess their safety, interaction with the system of OA, final metabolism, and optimization before their translation to clinics. While challenges remain, the unique ability of cell membrane-coated nanoparticles to evade immune clearance and target inflamed joint tissues offers real hope for developing more effective and precise OA therapies.

Introduction: Cancer remains a global challenge, driving the need for improved therapies and delivery systems. The customizable and controllable nature of 4D-printed, stimuli-responsive hydrogels underscores their potential in this context. By engineering these hydrogels to respond to specific tumor-associated stimuli, therapeutic efficacy can be enhanced while minimizing side effects, advancing the goals of precision oncology.

Areas covered: This review examines the types of stimuli used to design stimuli-sensitive hydrogels and their activation mechanisms. It summarizes recent advancements in 4D-printed, stimuli-responsive hydrogels for cancer treatment, assessing their potential, development stage, and limitations. The review also explores future directions, emphasizing the promise of 4D cancer models for drug screening due to their enhanced physiological complexity. Literature was sourced from CAS SciFinder, PubMed, and Google Scholar, focusing on studies from the past 10 years.

Expert opinion: 4D hydrogels offer a novel approach to personalized cancer therapy but are still in the early stages of development. Continued research into innovative stimuli-responsive polymers with suitable rheological properties for 3D printing is essential. Among emerging strategies, NIR-responsive 4D hydrogels, especially when combined with temperature-responsive systems, appear the most advanced and promising. Ongoing studies are vital to establish their role in precision oncology and translational medicine.

Introduction: Small airway dysfunction affects 50-90% of asthmatic patients, leading to airway remodeling, worsening symptoms, and quality of life. Targeting small airway dysfunction with inhaled extrafine formulations, with a mass median aerodynamic diameter < 2 µm, is crucial. Triple extrafine fixed-dose combination with inhaled corticosteroids (ICS), long-acting β₂-agonists (LABA), and long-acting muscarinic antagonists (LAMA) been approved for uncontrolled asthma, supported by TRIMARAN and TRIGGER randomized controlled trials (RCT). However, while RCTs offer valuable efficacy and safety data under controlled conditions, findings need to be combined with real-world evidence (RWE).

Areas covered: This narrative review assessed the impact of triple extrafine fixed-dose combination in asthma, integrating RCTs and RWE findings. Post-hoc analyses of RCTs and preliminary gray literature were also considered.

Expert opinion: RCTs and RWE showed significant overlap in outcomes for triple extrafine fixed-dose combination, although differing in some crucial patient characteristics (e.g. smoking status). Triple extrafine fixed-dose combination might be more effective in patients with persistent airflow limitation by targeting small airway dysfunction. However, further RCTs and RWE are needed to address remaining gaps, such as the determinants of response to medium-strength triple extrafine fixed-dose combination vs. high-strength ICS/LABA and to high-strength triple extrafine fixed-dose combination vs. open triple therapy.