Expert Opin Drug Deliv
· 2025 Nov · PMID 40923715
·
Publisher ↗
INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a promising treatment option for hematological malignancies. Despite its curative potential, it faces clinical challenges, including relapse and graft-versu...INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a promising treatment option for hematological malignancies. Despite its curative potential, it faces clinical challenges, including relapse and graft-versus-host disease (GVHD). Systemic toxicity due to chemotherapy is a significant problem in patients with hematological malignancies. Stem cell-based drug delivery can precisely deliver drugs to tumor sites, thereby increasing local drug toxicity, which may alleviate relapse and systemic toxicity. AREAS COVERED: This review integrates and critically examines the recent clinical advances in HSCT and its challenges. Autologous HSCT is constrained by the risk of relapse, whereas allogeneic HSCT is limited by donor availability and GVHD complications. Additionally, we highlight both the immunomodulation of mesenchymal stem cells (MSCs) in GVHD and the therapeutic potential of induced pluripotent stem cells (iPSCs). Furthermore, we explored stem cell-based drug delivery systems focusing on three primary strategies: (1) stem cells as intrinsic carriers, (2) stem cell-derived extracellular vesicles (EVs), and (3) stem cell membrane-derived biomimetic vesicles. EXPERT OPINION: While stem cell therapies hold promise, issues include the heterogeneity of stem cell sources, complexity of the cultivation process, and long-term safety issues. Future research should focus on large-scale technologies, stem cell engineering techniques, and combination therapies to facilitate clinical translation.
Khan S, Gull A, Akhtar M
… +5 more, Gull B, Najmi AK, Parveen R, Ali J, Khan S
Expert Opin Drug Deliv
· 2025 Nov · PMID 40913551
·
Publisher ↗
INTRODUCTION: The potential of nanomedicine in alleviating different disorders is immense, but its clinical translation rate is severely debilitated, despite promising preclinical study outcomes. For therapeutically succ...INTRODUCTION: The potential of nanomedicine in alleviating different disorders is immense, but its clinical translation rate is severely debilitated, despite promising preclinical study outcomes. For therapeutically successful targeted delivery of nanomedicines, it is crucial to understand why well-designed nanomedicines often fail during clinical trials. AREAS COVERED: This review comprehensively explores the multifactorial reasons behind the poor clinical success rate of nanomedicines, including pathophysiological complexity, limitations in statistical analysis, inadequate animal models, variability in the EPR effect, and manufacturing challenges. Special focus is placed on the misinterpretation and misuse of statistical tools in preclinical studies, which significantly reduces data interpretation and clinical predictability. The review is based on an in-depth literature survey of recent advances and failures in nanomedicine translation, with an emphasis on incorporating simulation models and synthesized data to overcome the challenges of statistics. EXPERT OPINION: Addressing translational gaps requires a multidisciplinary approach, refined preclinical models, robust statistical frameworks, and adaptive clinical designs that are essential. Innovative tools, such as CTGAN and personalized trial strategies, can bridge the preclinical-clinical divide. To realize the full potential of nanomedicine, it is crucial to resolve foundational issues in experimental design, data interpretation, analytical frameworks, and regulatory compliance.
Dalabehera M, Subudhi RN, Boateng J
… +7 more, Choonara YE, Chaudhari S, Chellappan DK, Kanojia N, Mnqiwu K, Singh TG, Negi P
Expert Opin Drug Deliv
· 2025 Nov · PMID 40891288
·
Publisher ↗
INTRODUCTION: Among the many ongoing difficulties, infections present significant clinical hurdles due to the rapid development of resistance, recurrent episodes, and the limited effectiveness of conventional therapies....INTRODUCTION: Among the many ongoing difficulties, infections present significant clinical hurdles due to the rapid development of resistance, recurrent episodes, and the limited effectiveness of conventional therapies. In recent decades, metallic nanoparticles (MNPs) and lipid nanoparticles (LNPs) have shown a specific impact (>84% biofilm inhibition in preclinical models) by addressing the critical challenges of mitigating drug side effects and multidrug resistance (MDR). AREAS COVERED: This paper provides an in-depth overview of synthesis, fabrication, mechanistic insights, preclinical and clinical practices for MNPs and LNPs, discussing and highlighting their therapeutic efficacy against resistant species over traditional methods. The literature was sourced from peer-reviewed journals and databases, including PubMed, Scopus, Web of Science, WIPO, and Clinical Trials up to May 2025. EXPERT OPINION: In this portion the potential of hybrid MNP-LNP systems with surface modification enables functionalization by targeting ligands and more specific binding toward fungal cells to enhance the therapeutic index. In addition, combining drug-loaded MNPs and LNPs with artificial intelligence (AI), photodynamic, gene, or immune therapies offers a comprehensive and innovative solution for MDR . However, addressing regulatory complexity still needs to be considered toward optimizing the stability and scalability of MNPs and LNPs for clinically meaningful translation.
Expert Opin Drug Deliv
· 2025 Nov · PMID 40889121
·
Publisher ↗
INTRODUCTION: Elevated levels of reactive oxygen species (ROS), which are key mediators in different pathophysiological conditions, provide a unique opportunity for achieving targeted drug delivery. As such, ROS-responsi...INTRODUCTION: Elevated levels of reactive oxygen species (ROS), which are key mediators in different pathophysiological conditions, provide a unique opportunity for achieving targeted drug delivery. As such, ROS-responsive liposomes that undergo variable structural changes have emerged as promising tools for drug delivery purposes. These approaches show strong prospects for enhancing the selectivity of delivery to diseased cells through nanoparticle activation by aberrant ROS concentrations. AREA COVERED: This review describes elegant strategies for engineering ROS-responsive liposomes through lipid switch oxidation. These platforms exhibit improvements, including ROS-triggered release of encapsulated cargo, detachment of medicinal agents through prodrug strategies, programmed activation of cellular delivery, and photodynamic therapies. We describe how lipid switch design features can be leveraged to achieve these varying applications. EXPERT OPINION: ROS-responsive liposomes provide an adaptable approach for targeted therapy in environments associated with higher oxidative stress. We discuss how the attributes of each platform position these systems for overcoming practical issues, including stability, scalability, and clinical efficacy, as well as strategies for maximizing properties through continued innovation. In general, ROS-responsive liposome stability must be carefully tuned to be sufficiently stable to survive circulation but become activated within a window of ROS concentration that differentiates between diseased and healthy cells.
Wang H, Wei G, Yin J
… +3 more, Yang M, Tong L, Wang JW
Expert Opin Drug Deliv
· 2025 Nov · PMID 40883963
·
Publisher ↗
INTRODUCTION: The heart is a highly dynamic organ with limited regenerative capacity and a unique microvascular environment, which restricts the accumulation and retention of systemically administered therapeutics. Despi...INTRODUCTION: The heart is a highly dynamic organ with limited regenerative capacity and a unique microvascular environment, which restricts the accumulation and retention of systemically administered therapeutics. Despite notable progress in nanomedicine and targeted drug delivery technologies, achieving efficient and specific drug delivery to cardiac tissue remains a formidable challenge. AREAS COVERED: Extracellular vesicles (EVs) represent a novel therapeutic strategy for cardiovascular diseases, offering a versatile platform to integrate therapeutics, targeting moieties, and sensing elements for the detection, prevention, and treatment of cardiovascular diseases (CVD). This review highlights the recent progress in employing EVs as carriers for targeted myocardial drug delivery and explores their potential for clinical translation. A literature search was conducted using PubMed, focusing on studies categorized under EVs, cardiovascular diseases, and myocardium-targeted delivery. Current progress of EVs in clinical applications was evaluated based on the data from ClinicalTrials.gov. EXPERT OPINION: EVs offer significant promise for clinical myocardial drug delivery. Some key considerations for clinical application of EVs include modulating immune clearance, establishing scalable production with stringent quality control, and refining surface engineering strategies. Facilitating EV clinical translation requires focused strategies to overcome current barriers, especially by integrating bioengineering and biomaterial-based targeting to enhance myocardial delivery efficiency.
Expert Opin Drug Deliv
· 2025 Nov · PMID 40875977
·
Publisher ↗
INTRODUCTION: Propolis is a gum-resinous compound produced by bees for hive protection. It displays complex chemical composition, dependent on the plant sources, and important biological activities, contributing to a wid...INTRODUCTION: Propolis is a gum-resinous compound produced by bees for hive protection. It displays complex chemical composition, dependent on the plant sources, and important biological activities, contributing to a wide range of pharmacological effects (e.g. antimicrobial, anti-inflammatory, healing and immunostimulant). Propolis shows poor aqueous solubility and low bioavailability. Thus, delivery systems have been proposed for the administration of propolis by different routes like oral, buccal, topical, local, vaginal, transmucosal, nasal, endodontics and intra-periodontal pocket. AREAS COVERED: From extracts and ointments, formulations for propolis delivery improved their physicochemical properties. The use of biocompatible, biodegradable, environmentally responsive materials, nanotechnology, and propolis by-product resulted in smart systems: films, micro/nanoparticles, lipid systems, carbon nanotubes, emulsion, and self-emulsifying systems, bioadhesive and environmentally responsive systems, microneedles, liquid crystals, sensors and electrospun fibers. EXPERT OPINION: Ensuring the efficacy and safety of propolis requires characterization, standardization, and quality control. Challenges like composition variability, limited bioavailability, and inconsistent extraction hinder its optimal use. Nanotechnology improves bioavailability and controlled release, while emerging strategies like microneedles and 3D/4D printing enhance precision and versatility. By integrating nanotechnology and additive manufacturing, researchers can develop safer, more effective delivery systems, expanding propolis applications and fostering innovation in pharmaceutical and biomedical fields.
Lu Y, Essadki-Aittaji I, Gao J
… +8 more, Abraham AM, Anjani QK, Cobo-González AB, Iglesias-Martín F, Vora LK, Millán-Jiménez M, Larrañeta E, Domínguez-Robles J
Expert Opin Drug Deliv
· 2026 Jan · PMID 40855833
·
Publisher ↗
INTRODUCTION: Pain is a widespread global health issue, significantly affecting quality of life and contributing to disability. It is estimated that between 20% and 30% of the global population suffer from some form of n...INTRODUCTION: Pain is a widespread global health issue, significantly affecting quality of life and contributing to disability. It is estimated that between 20% and 30% of the global population suffer from some form of non-cancer chronic pain. Around 80% of surgical patients report postoperative acute pain, with less than 50% achieving adequate pain control. Despite these statistics, the management of pain still remains a significant challenge for clinicians, with many patients experiencing poorly controlled pain or adverse effects related to analgesic medication. AREAS COVERED: This literature review outlines current pain management strategies, focusing on non-oral postoperative pain therapies, including injectable drug delivery systems (such as in situ forming implants, micro- and nano-based formulations) and implantable drug delivery systems. Emphasis is placed on solid implantable devices designed for sustained drug delivery, which can offer more efficient localized drug delivery at the pain site. EXPERT OPINION: While pharmacological treatments, including oral opioids and nonsteroidal anti-inflammatory drugs, are commonly used, implantable controlled release systems are emerging as more effective alternatives. These systems provide localized pain relief with reduced systemic exposure, minimizing side effects, opioid use, and the risk of addiction, offering a promising solution for improved postoperative pain management.
Expert Opin Drug Deliv
· 2025 Nov · PMID 40787941
·
Publisher ↗
INTRODUCTION: Breast cancer, a malignancy characterized by high recurrence and mortality rates, faces critical bottlenecks in conventional therapies including systemic toxicity and insufficient drug concentration at lesi...INTRODUCTION: Breast cancer, a malignancy characterized by high recurrence and mortality rates, faces critical bottlenecks in conventional therapies including systemic toxicity and insufficient drug concentration at lesion sites. Dissolving microneedles (DMNs) are micron-scale arrays fabricated from biodegradable materials. By leveraging their unique capability to penetrate the epidermal barrier and deliver drugs with precision, DMNs pioneer a novel therapeutic approach for breast cancer treatment. AREAS COVERED: This review provides new insights and directions for breast cancer research by systematically examining the latest advances in DMNs for breast cancer treatment. We comprehensively analyze DMNs mechanisms for localized delivery of chemotherapeutics, targeted degraders, immunomodulators, and gene editors, while assessing synergistic combinations with nanotechnology, physical therapies, and immunotherapy to overcome drug resistance and immunosuppression. EXPERT OPINION: Based on the literature review, DMNs demonstrate potential for breast cancer therapy through localized multi-agent delivery and combination strategies, significantly improving treatment efficacy for superficial tumors while minimizing systemic exposure.
Salamone S, Manin S, Musumeci T
… +4 more, Carbone C, Bonaccorso A, Rodriguez-Rodriguez R, Pignatello R
Expert Opin Drug Deliv
· 2025 Nov · PMID 40755382
·
Publisher ↗
INTRODUCTION: There is growing evidence about the efficacy of natural compounds and peptides as central-acting anti-obesity drugs; on the other hand, their pharmacokinetic profile often hampers the clinical application....INTRODUCTION: There is growing evidence about the efficacy of natural compounds and peptides as central-acting anti-obesity drugs; on the other hand, their pharmacokinetic profile often hampers the clinical application. In this narrative review, the critical role of nanomedicine and peptide conjugation is reported as a promising strategy to overcome these limits. AREAS COVERED: The focus areas were centrally acting drugs for obesity, providing context about pathways involved and past and currently approved medications, pointing out their limits. The last 10 years research was analyzed to collect the progress in central-acting anti-obesity drugs and the new potential strategies (nanomedicine and conjugation), with attention on natural compounds and peptides. EXPERT OPINION: Based on literature review, nanocarriers and conjugation strategies can offer targeted delivery of both natural molecules and peptides, enhancing their therapeutics, improving cellular uptake, and regulating metabolism and inflammatory pathways. The choice of the proper administration route, along with a delivery strategy significantly impacts the pharmacokinetics and therapeutic outcomes of compounds delivered through nanomedicines and encourages their translation 'from bench to bedside.'
Gato-Diaz U, Concheiro A, Alvarez-Lorenzo C
… +1 more, Blanco-Fernandez B
Expert Opin Drug Deliv
· 2025 Oct · PMID 40739734
·
Publisher ↗
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 potent...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.
Fogliano C, Rigon L, Chaudhuri KR
… +8 more, Popławska-Domaszewicz K, Falup-Pecurariu C, Murasan I, Guerra A, Garon M, Odin P, Hattori N, Antonini A
Expert Opin Drug Deliv
· 2025 Oct · PMID 40734379
·
Publisher ↗
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 dop...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.
Gao F, Sun AR, Mao X
… +4 more, Kokil GR, Crawford R, Kumeria T, Prasadam I
Expert Opin Drug Deliv
· 2025 Oct · PMID 40734328
·
Publisher ↗
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 disea...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.
Nicoletti L, Coletto M, Stola GP
… +7 more, Paoletti C, Marcello E, Testore D, Tivano F, Zoso A, Mattu C, Chiono V
Expert Opin Drug Deliv
· 2025 Oct · PMID 40720801
·
Publisher ↗
INTRODUCTION: Cardiovascular diseases (CVDs) account for one-third of the global mortality rate. RNA therapeutics have emerged as a promising tool to modulate gene expression and molecular pathways in CVDs. However, thei...INTRODUCTION: Cardiovascular diseases (CVDs) account for one-third of the global mortality rate. RNA therapeutics have emerged as a promising tool to modulate gene expression and molecular pathways in CVDs. However, their clinical translation is hampered by instability, immunogenicity, and inefficient delivery across anatomical and physiological barriers. AREAS COVERED: This review critically examines emerging strategies for the targeted delivery of RNA therapeutics to the heart, critically analyzing systemic and local barriers. Emphasis is placed on chemical modifications of RNA molecules, encapsulation, biomimetic, and targeted approaches to enhance tissue and cellular targeting. The analysis is supported by a structured literature search encompassing preclinical and translational studies. Challenges to the clinical translation of RNA delivery are highlighted. Research and review articles, as well as clinical trials published between 2008 and 2024 were searched from PubMed, Web-of-Science, and ClinicalTrials.gov. EXPERT OPINION: Local delivery systems are crucial to improve RNA retention and diffusion through the extracellular matrix (ECM), while cell-type - specific strategies targeting cardiomyocytes and fibroblasts can enhance precision within a heterogeneous cardiac microenvironment (CME). These approaches represent a fundamental basis for the rational design of RNA therapeutics to overcome biological barriers and enable efficient, targeted delivery to cardiac tissue.
Reychler G, Audag N, Cnockaert P
… +3 more, Jamar F, Danse E, Hox V
Expert Opin Drug Deliv
· 2025 Oct · PMID 40711547
·
Publisher ↗
INTRODUCTION: Nasal irrigations are a longstanding modality of treatment. Mechanical and of the nasal cavities and paranasal sinuses are frequently conflated under the principle of nasal irrigations even if the objecti...INTRODUCTION: Nasal irrigations are a longstanding modality of treatment. Mechanical and of the nasal cavities and paranasal sinuses are frequently conflated under the principle of nasal irrigations even if the objectives are different. AREAS COVERED: The aims and principles of these two different modalities are described in the first part of the paper. In the second part, the literature is summarized based on the data related to the clinical efficacy of the nasal irrigation and on the results of the studies assessing the physical efficacy of the delivery. EXPERT OPINION: Although abundant, the literature does not provide strong enough evidence about the optimal nasal irrigation modality. There is a genuine need for a clear definition of terms and evidence-based recommendations on the techniques that should be proposed to patients according to specific clinical objectives. The authors proposed a new terminology to distinguish between nasal clearance irrigation and nasal drug irrigation.
Expert Opin Drug Deliv
· 2025 Oct · PMID 40625242
·
Publisher ↗
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 n...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 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 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.