Drug Delivery最新文献

Lung cancer is the second most common cancer worldwide, with persistently high morbidity and mortality rates. Despite years of research in the field, a complete cure for this disease remains elusive. Current clinical treatment options primarily include chemotherapy, surgery, and targeted drugs. However, these treatments are often limited by the highly metastatic nature of lung tumors and the development of drug resistance, resulting in suboptimal therapeutic outcomes. Ferroptosis is an iron-dependent cell death mechanism driven by lipid peroxidation, offers promising potential to overcome drug resistance in lung cancer. Recent advances in nanotechnology have enabled targeted delivery and precise regulation of ferroptosis pathways, addressing the limitations of conventional therapies. This review systematically summarizes current strategies utilizing nanomedicine to induce ferroptosis in lung cancer, with a focus on key molecular targets, such as GPX4, System Xc^-, and FSP1, as well as innovative delivery platforms including metal nanoparticles, nanozymes, and responsive liposomes. Unique challenges in pulmonary drug delivery, such as mucociliary clearance and oxidative microenvironments are also discussed, along with lung cancer-specific solutions like inhalable systems and tumor microenvironment remodeling. Furthermore, we compare ferroptosis nanotherapies across different cancers to highlight the distinctive innovations in lung cancer. This article provides a comprehensive overview of recent progress and proposes optimized strategies to enhance therapeutic efficacy, offering insights into the translational potential of ferroptosis-based nanomedicine in lung cancer treatment.

Despite their anti-inflammatory activity, corticosteroids are limited in clinic due to poor selectivity and their side effects. The ability to cross biological barriers makes them powerful yet unspecific, leading to toxicity and a low therapeutic index that limits their chronic use in autoimmune, inflammatory, and infectious diseases. It is needed another approachfor innovative targeted delivery strategies. This study aimed at investigating if the dexamethasone conjugation to Avidin-Nucleic-Acid-NanoASsembly (ANANAS) could allow its selective lung release in the bleomycin-induced pulmonary fibrosis model. Since recent evidence showed a selective ANANAS accumulation in macrophage lysosomes in a liver fibrosis model, an acid-sensitive hydrazone linker was used to facilitate dexamethasone release into pulmonary macrophages, key players in lung fibrosis. Systemic ANANAS-Dex administration in healthy mice showed no dexamethasone release in plasma or peripheral organs, with delivery exclusively targeting the liver, independent of the health status. While this confirmed the nanocarrier safety, it underscored the influence of the administration route, rather than the disease state, on ANANAS-Dex tropism. The study on intranasal administration highlighted that: 1) free Dex circulates in the bloodstream, while ANANAS keeps the drug confined in the lungs; 2) ANANAS-Dex results in sustained drug release in the lungs, enhancing the lungs/plasma-peripheral organs ratio; 3) fibrotic mice exhibited prolonged kinetics and macrophage targeting. Based on the biodistribution and pharmacokinetics studies, it is possible to achieve controlled and safe steroid release in lung disorders, reducing systemic toxicity and potentially enhancing clinical compliance.

While nurses report challenges with the manual administration of large-volume subcutaneous drugs, these challenges and potential solutions are not captured in the literature. In this cross-sectional study, 45 nurses with experience administering large-volume subcutaneous biologics completed an 18-item survey about preferences for syringes vs. on-body delivery systems. 100% responded that an on-body delivery system seemed easy to learn and use and preferable to syringes. In a drug delivery scenario including comprehensive administration details and assuming equivalent safety and efficacy, 97.78% preferred the on-body delivery system to a daratumumab/hyaluronidase syringe. In the total sample, this preference was primarily attributed to (1) reduced nurse effort due to hands-free delivery, (2) decreased patient pain due to a thinner needle, (3) elimination of needlestick injuries due to a hidden needle, and (4) increased clinic efficiency due to hands-free delivery. 95.56% felt that the on-body delivery system would improve clinic throughput better than syringes. Nurses reported that an on-body delivery system would be easy to learn and use and would improve clinic efficiency and safety. They underscored the importance of decreasing nurse physical burden, needlestick injuries, and patient needle phobia. Contrary to the assumption that speed is paramount, nurses prioritized reducing effort, enhancing administration safety, and improving patient comfort over injection speed.

Nowadays, pulmonary diseases (PDs) are among the leading causes of mortality worldwide. Conventional therapeutic approaches exhibit disappointing efficacies due to difficulty in drug delivery and systemic cytotoxicity. In recent years, novel formulations of therapeutic drugs rised as alternatives for clinical treatment. Among them, cell-derived drug delivery systems (CDDSs) have garnered attention for their potential in treating PDs. By harnessing the innate migratory capabilities, barrier-crossing potential, high biocompatibility, and substantial drug-loading capacity of cell derivatives, CDDSs offer a promising approach for PD treatment. However, there was no systemic report in summarizing CDDSs in PDs. In this review, We first examined the biological properties and therapeutic advantages of various CDDSs in the context of PDs, including red blood cells (RBCs), stem cells, platelets, macrophages, neutrophils, tumor cells, microalgae, extracellular vesicles (EVs) and biomimetic cell membrane. We then discussed common preparation strategies and different modification methods of CDDSs. Finally, we summarized the current therapeutic advancements of CDDSs in multiple PDs. We hope this review serves as a valuable reference for utilizing CDDSs in the treatment of PDs and other diseases.

Nanoparticles-based gene delivery has emerged as a promising approach for the treatment of genetic diseases based on efficient delivery systems for therapeutic nucleic acids (NAs) into the target cells. For pulmonary diseases such as cystic fibrosis (CF), chronic obstructive pulmonary diseases (COPD), infectious disease or lung cancer, aerosol delivery is the best choice to locally deliver NAs into the lungs. It is, therefore, important to investigate the effects of nebulization conditions on the efficiency of delivery. To this purpose, the non-viral vector branched polyethyleneimine (b-PEI, 25 kDa) was investigated for plasmid delivery by aerosol. Two types of nebulizers, jet nebulizer and mesh nebulizer, were compared regarding the properties of the nanoparticles (NPs) formed, the efficiency of NAs delivery in vitro and in vivo models and the pulmonary deposition. The results indicate that the mesh nebulizer has a better gene delivery performance than the jet nebulizer in this application. This superiority was demonstrated in terms of size, concentration, distribution of NPs and efficiency of NAs delivery. However, pulmonary deposition appears to be similar regardless of the nebulizer used, and the difference between the two systems lies in the inhalable dose. These results underline the crucial role of nebulization techniques in optimizing aerosol-mediated gene delivery by b-PEI and highlight the potential of mesh nebulizers as promising tools to improved gene therapy. Therefore, the comparison must be performed for each gene therapy formulation to determine the most suitable nebulizer.

The tympanic membrane (TM) forms an impenetrable barrier to medical therapies for middle ear (ME) diseases like otitis media. By screening a phage-displayed peptide library, we have previously discovered rare peptides that mediate the active transport of cargo across the intact membrane of animals and humans. Since the M13 filamentous bacteriophage on which the peptides are expressed are large (nearly 1 µm in length), this offers the possibility of noninvasively delivering drugs, large drug packages, or gene therapy to the ME. To evaluate this possibility, EDC chemistry was employed to covalently attach amoxicillin, or neomycin molecules to phage bearing a trans-TM peptide, as a model for large drug packages. Eight hours after application of antibiotic-phage to the TM of infected rats, ME bacterial titers were substantially reduced compared to untreated animals. As a control, antibiotic was linked to wild-type phage, not bearing any peptide, and application to the TM did not affect ME bacteria. The results support the ability of rare peptides to actively deliver pharmacologically relevant amounts of drugs through the intact TM and into the ME. Moreover, since bacteriophage engineered to express peptides are viral vectors, the trans-TM peptides could also transport other viral vectors into the ME.

Glaucoma is a multifactorial neurodegenerative disease that affects the retina and optic nerve. The aim of this work was to reach different therapeutics targets by co-encapsulating three neuroprotective substances with hypotensive (latanoprost), antioxidant (melatonin) and anti-inflammatory (ketorolac) activity in biodegradable poly (lactic-co-glycolic acid) (PLGA) microspheres (MSs) capable of releasing the drugs for months after intravitreal injection, avoiding the need for repeated administrations. Multi-loaded PLGA MSs were prepared using the oil-in-water emulsion solvent extraction-evaporation technique and physicochemically characterized. PLGA 85:15 was the polymer ratio selected for the selected formulation. Tri-loaded MSs including vitamin E as additive showed good tolerance in retinal pigment epithelium cells after 24 h exposure (>90% cell viability). The final formulation (KMLVE) resulted in 33.58 ± 5.44 µm particle size and drug content (µg/mg MSs) of 39.70 ± 5.89, 67.28 ± 4.17 and 7.51 ± 0.58 for melatonin, ketorolac and latanoprost respectively. KMLVE were able to release in a sustained manner the three drugs over 70 days. KMLVE were injected at 2 and 12 weeks in Long-Evans rats (n = 20) after the induction of chronic glaucoma. Ophthalmological tests were performed and compared to not treated glaucomatous (n = 45) and healthy (n = 17) animals. Treated glaucomatous rats reached the lowest intraocular pressure, enhanced functionality of bipolar and retinal ganglion cells and showed greater neuroretinal thickness by optical coherence tomography (p < 0.05) compared to not treated glaucomatous rats at 24 weeks follow-up. According to the results, the tri-loaded microspheres can be considered as promising controlled-release system for the treatment of glaucoma.

Liver diseases, particularly chronic conditions leading to cirrhosis and hepatocellular carcinoma, represent a major global health burden with high mortality rates, necessitating innovative diagnostic and therapeutic approaches. Ultrasound-targeted microbubble destruction (UTMD) technology has emerged as a promising theranostic platform, combining enhanced contrast imaging with targeted drug/gene delivery capabilities. When activated by ultrasound, these microbubbles exhibit unique biophysical behaviors that significantly improve drug penetration, tissue perfusion, and site-specific delivery. This review comprehensively examines recent advancements in UTMD-based strategies for liver disease management, including microbubble design and imaging-targeted functionalization, and mechanisms of ultrasound-enhanced drug delivery, especially emerging theranostic applications. We further discuss the underlying biophysical principles governing microbubble-ultrasound interactions and their translational potential, providing insights for developing next-generation precision medicine approaches for hepatic disorders.

Antibody therapeutics have emerged as a cornerstone in modern biopharmaceutical development, revolutionizing treatments across diverse diseases. Recent breakthroughs in antibody discovery technologies, particularly single B-cell sorting and high-throughput sequencing, have significantly enhanced the ability to identify and isolate potent therapeutic antibodies. Despite these advances, widespread adoption of monoclonal antibody (mAb) therapies faces substantial challenges, including complex manufacturing processes, high production costs, and stringent cold-chain storage requirements. A promising solution to these limitations is nucleic acid-encoded antibody delivery, which enables in vivo production of functional antibodies. This technology delivers nucleotide sequences encoding mAbs instead of the antibody proteins themselves, effectively turning the body into a bioreactor for antibody production. By bypassing the complex purification and quality control processes associated with traditional recombinant protein production, this approach offers a more streamlined and potentially cost-effective alternative. Herein, we review current nucleic acid-based antibody delivery platforms, highlighting the unique advantages and technical challenges. We provide an in-depth analysis of the latest advancements in this field, including both viral and non-viral delivery methods, and discuss their implications for next-generation antibody therapeutics. We also examine the potential applications in infectious diseases and cancer immunotherapy, alongside regulatory and safety considerations for clinical translation. We aim to provide valuable insights and guidance for researchers and clinicians in advancing novel antibody-based therapies.

Efficient messenger ribonucleic acid (mRNA) delivery to the retina remains challenging. This study investigated the effects of various polyethylene glycol (PEG) derivatives on the stability and uptake of cationic lipid-based mRNA lipoplexes in vitro and assessed the delivery of selected formulations to the canine retina. We present an optimized workflow for formulating mRNA lipoplexes in pure water, achieving high encapsulation efficiency. PEGylation enhanced stability of lipoplexes, particularly with PEG-DMG or hyaluronan conjugated to PEG-DPPE (HA-PEG-DPPE), maintaining size and zeta potential for 48 hours. RNA in situ hybridization (RNA-ISH) confirmed efficient internalization of PEGylated mRNA lipoplexes by cultured RAW264.7 and ARPE19 cells, though corresponding protein expression varied between cell lines. Analysis at 24 hours post-intravitreal injection of PEG-DMG- and HA-PEG-DPPE-stabilized enhanced green fluorescent protein (eGFP) mRNA lipoplexes revealed limited mRNA accumulation in inner retinal layers. In contrast, 24 hours after their subretinal administration, eGFP mRNA was detected in all retinal cell types, including photoreceptors, with accumulation comparable to endogenous rhodopsin (RHO) mRNA levels. eGFP protein expression, though, was limited to the retinal pigment epithelium (RPE). At 72 hours post-subretinal delivery, eGFP mRNA and protein persisted in the RPE. However, a marked reduction in eGFP levels was seen in other retinal layers, displaying a patchy pattern. Similarly, eGFP protein exhibited a patchy distribution across retinal layers outside the RPE. Furthermore, distinct differences in the cell types expressing the eGFP protein were observed between the two PEGylated mRNA lipoplex formulations. The data suggest that transfection efficiency in retinal cells is influenced by both intracellular processing of mRNA lipoplexes and their uptake, with the former playing a predominant role.