Expert opinion on drug delivery最新文献

Introduction: Colorectal cancer (CRC) is a major cause of cancer mortality, with poor outcomes driven by the tumor microenvironment (TME). Heterogeneous cancer-associated fibroblasts (CAFs) remodel the extracellular matrix (ECM), suppress immunity, and secrete cytokines that promote progression and resistance. As both barriers and therapeutic targets, CAFs are central to strategies aimed at overcoming treatment limitations in CRC.

Areas covered: We examine how CAF heterogeneity, with predominantly pro-tumorigenic but occasionally tumor-restraining functions, contributes to drug delivery resistance. This review highlights nanodrug delivery systems that integrate CAF targeting as a promising strategy to enhance therapeutic efficacy. Approaches include passive and active targeting of ECM degradation to improve drug penetration, advanced carriers for CAF reprogramming, CAF markers, and multifunctional platforms combining chemo- and immunotherapy. Literature was identified through PubMed, Web of Science, Scopus, and ClinicalTrials.gov searches up to September 2025, focusing on CAF biology, nanodrug delivery, and CRC translation.

Expert opinion: CAF-targeted nanodrug delivery offers a transformative opportunity to address long-standing barriers in CRC therapy. Future advances will depend on the integration of multi-omics CAF subtyping, rational combination regimens, and clinically scalable nanocarriers to translate these strategies into a lasting clinical benefit.

Introduction: Plant-derived extracellular vesicles (PDEVs) have emerged as natural nanocarriers with promising applications in drug delivery and precision medicine. Secreted by plant cells, PDEVs facilitate intercellular communication by transporting metabolites. Unlike conventional liposomes and mammalian-derived EVs, PDEVs demonstrate excellent biocompatibility, stability, and the ability to cross biological barriers without inducing inflammatory or cytotoxic effects. Their capacity to encapsulate both hydrophilic and hydrophobic therapeutic agents highlight their versatility as targeted delivery platforms.

Areas covered: This review summarizes PDEV biogenesis in comparison with mammalian-derived EVs and emphasizes characterization techniques and the role of lipid components in drug delivery efficacy. Drug loading strategies are critically examined with respect to their efficiency, advantages, and limitations. Advances in engineering, including surface modification and hybrid vesicle formation, are discussed to enhance targeting precision, circulation stability, and controlled drug release. Therapeutic potential and synergetic application in disease prevention and management are evaluated, alongside key considerations such as storage stability, current limitations, and opportunities for clinical translation.

Expert opinion: PDEVs represents a promising platform for drug delivery and precision medicine. Although large-scale production, standardization and long-term stability remain challenges, recent innovations in loading strategies and engineering approaches demonstrate significant potential to overcome these barriers and accelerate clinical translation.

Introduction: Helicobacter pylori infections demand innovative therapeutic strategies due to rising antibiotic resistance. This review consolidates recent advances in nanoparticle (NP)-based drug delivery systems engineered to optimize antimicrobial efficacy against H. pylori.

Areas covered: We critically examine the design, functionality, and performance of metallic, polymeric, lipid-based, and biomimetic nano-carriers, highlighting their advantages over conventional antibiotic delivery.

Expert opinion: Key innovations include: Lipid-based systems enabling synergistic co-delivery of hesperidin (0.064 μg mL⁻¹) and clarithromycin (0.15 mg mL⁻¹) for enhanced drug bioavailability; Polymeric NPs (e.g. rhamnolipid-chitosan hybrids) achieving deep biofilm penetration ( > 99% eradication) within gastric mucus at minimal inhibitory concentrations (32-132 µg/mL). These nanoplatforms demonstrate precision gastric-mucosa targeting, improved penetration of biological barriers, and controlled antimicrobial release. By maximizing localized drug delivery while minimizing systemic exposure, NP-based systems address critical limitations of current therapies, including resistance and microbiota disruption. We further emphasize the need for clinical validation to translate these delivery technologies into standardized treatments, ultimately reducing the global burden of H. pylori-associated diseases.

Introduction: Plant-derived extracellular vesicles (PEVs) have shown significant promise as a novel oral delivery system for nucleotide-based drugs. The successful oral delivery of nucleotide drugs using PEVs paves the way for developing innovative nucleotide delivery systems in terms of inflammatory bowel disease, cancer and metabolic diseases treatment. By utilizing surface and other engineering modifications, PEVs can circumvent the challenges of oral administration posed by the gastrointestinal barrier and enzymatic degradation.

Areas covered: This review covers PEVs as oral nucleotide carriers, focusing on their anti-inflammatory, anticancer, and metabolic disease applications. It includes engineered modification methods (ligand, polymer modification, fusion) and nucleotide delivery application. This review searched for keywords using literature retrieval websites such as PubMed, Embase, and Google Scholar.

Expert opinion: This review introduces recent advancements of PEV-based technologies focused on ingestible nucleotide delivery, not only contributing valuable theoretical insights but also offering practical guidance for future precision medicine and drug development by PEVs. However, the current existence of regulatory ambiguity and low production efficiency has hindered the clinical translation and large-scale application of PEV-based oral nucleotide delivery systems.

Introduction: Despite high vaccination coverage, pertussis remains endemic, and epidemic cycles continue to occur every 3-5 years, illustrating the shortcomings of current vaccination strategies. Unlike current vaccines, especially acellular pertussis vaccines, which prevent disease for short duration but do not prevent nasal colonization by the etiological agent Bordetella pertussis, natural infection can induce durable immunity against disease and infection. Accordingly, live-attenuated nasal pertussis vaccine candidates have been developed to mimic the immunogenicity of natural infection without causing disease.

Areas covered: We summarize the current status of live-attenuated nasal pertussis vaccines based on a literature search with keywords 'pertussis vaccine,' 'live,' and 'attenuated.' These candidates were designed based on different strategies, including dependence on critical metabolites for bacterial growth, genetic attenuation of virulence, and modification of immunomodulatory properties of Bordetella.

Expert opinion: Only vaccines based on genetic attenuation of virulence have reached clinical development thus far. The most advanced candidate is BPZE1, which has successfully completed six clinical studies, demonstrating safety, systemic and mucosal immunogenicity, and the ability to prevent or substantially reduce B. pertussis infection. If BPZE1 is eventually adopted for global use, it will likely be a major breakthrough in the ultimate control of pertussis, which has plagued humanity for centuries.

Background: Acute lung injury (ALI) is a pathological condition characterized by diffuse lung injury. Excessive macrophage polarization to the M1 type in lung tissue plays a crucial role in the incidence and aggravation of ALI.

Research design and methods: Bilirubin (BR) has been applied as a therapeutic agent in various diseases due to its ability to regulate macrophage polarization. Based on the inherent engulfing of M1 macrophages toward xenobiotic nanomedicines, an inhalable BR nanomedicine was developed for the treatment of ALI. The BR nanoparticles (BRn) were first prepared using a one-step nanoprecipitation method, followed by surface modification with immunoglobulin G (IgG) at a 20% weight ratio to prepare BRn@IgG.

Results: Both nanoparticles exhibited excellent stability and enhanced antioxidative properties in aqueous phases. To gain the initiative, the IgG-modified nanoparticles could smartly bind to M1 macrophages, resulting in greatly improved BR delivery efficiency to macrophages and thus enhancing antioxidative, anti-inflammatory, and polarization-regulating effects compared to naked BRn. BRn@IgG evaded mechanical clearance from lung tissue and demonstrated prolonged retention in the pulmonary environment, thereby attaining the most potent therapeutic effect among all formulations in this study.

Conclusion: BRn@IgG could be considered a novel and effective therapeutic agent for the ALI treatment.

Introduction: Atrial cardiomyopathy (ACM) is characterized by complex interactions involving molecular, electrical, and structural abnormalities that predispose individuals to cardiac dysfunction and stroke. Current treatments are effective at managing the complications of ACM, but lack the ability to correct the underlying atrial substrate driving the disease state. Alternative treatment modalities are required to address this shortfall with viral-based delivery methods, particularly recombinant adeno-associated viral vectors (rAAVs), being at the forefront of filling this unmet need. Research in the design of rAAVs targeting the atrial myocardium has demonstrated robust atrial transduction with minimal toxicity. Despite the technology's promise, various biological, immunological, and economic obstacles continue to challenge the clinical translation of rAAVs targeting ACM.

Areas covered: In this review, the concept of ACM is summarized along with its common sequelae and current management. Following this, a basic overview of rAAV biology is provided alongside a narrative review of research investigating rAAV-based gene therapy targeting atrial myocardium in preclinical models.

Expert opinion: Gene therapies provide an opportunity to treat ACM at the root cause beyond the management of its sequelae. However, solutions aiming to improve vector design, manufacturability and suitability for ACM should be adopted to improve therapeutic efficacy and broaden patient accessibility.

Introduction: Viral diseases such as influenza, severe acute respiratory syndrome (SARS) caused due to coronaviruses (CoVs), Ebola, and acquired immunodeficiency syndrome (AIDS) caused due to human immunodeficiency virus (HIV) are still some of the major global causes of morbidity and mortality. Traditional antiviral therapies face limitations because of resistance development and toxicity. As a result, plant-derived medicines are gaining more attention for their therapeutic potential, owing to their lower toxicity and reduced likelihood of resistance development.

Areas covered: This review critically examines the antiviral properties of phytoconstituents like coumarins, steroids, and polysaccharides against various viruses. It discusses their integration with nanotechnology delivery systems to overcome bioavailability issues and highlights the need for translational studies to corroborate in vitro results.

Expert opinion: The convergence of phytotherapy and nanotechnology represents a promising frontier in antiviral drug development. While significant progress has been made in identifying active phytochemicals and formulating them with nanocarriers, more in-vivo data, clinical research, standardization efforts, and regulatory clarity are needed. This review may serve as a foundational resource for researchers aiming to develop innovative antiviral therapies based on natural compounds and nanotechnology-based delivery systems.