Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes

ACS Nano, Год журнала: 2024, Номер 18(10), С. 7455 - 7472

Опубликована: Фев. 28, 2024

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy diminished the formation of protein coronas (PCs) when they interact with matrices. PCs are broadly implicated in affecting fate NPs vivo vitro, yet few studies have investigated formed during interactions mucosa, especially mucus. In study, we constructed transferrin modified (Tf-NPs) as model explored mechanisms effects that had subsequent impact transcellular transport Tf-NPs. mucus-secreting cells, Tf-NPs adsorbed more proteins from mucus layers, which masked, displaced, dampened active targeting Tf-NPs, thereby weakening endocytosis efficiencies. mucus-free intracellular trafficking, enhanced transcytosis related functions. Inspired soft artificial biomimetic membranes, used mucin an "active PC" to precoat (M@Tf-NPs), limited negative impacts "passive PCs" interface improved favorable routes endocytosis. M@Tf-NPs associated endoplasmic reticulum-Golgi functions, prompting exocytosis. summary, shielded against absorption also could be employed spear break through barrier. These findings offer theoretical foundation design platform enhance efficiency oral-administered nanomedicines.

Язык: Английский

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Optimization, In Vitro, and In Silico Characterization of Theophylline Inhalable Powder Using Raffinose-Amino Acid Combination as Fine Co-Spray-Dried Carriers

Pharmaceutics, Год журнала: 2025, Номер 17(4), С. 466 - 466

Опубликована: Апрель 3, 2025

Background/Objectives: Dry powder inhalation is an attractive research area for development. Therefore, this work aimed to develop inhalable co-spray-dried theophylline (TN) microparticles, utilizing raffinose-amino acid fine carriers intended asthma therapy. The study addressed enhancing TN’s physicochemical and aerodynamic properties ensure efficient lung deposition. Methods: process involves spray-drying each formulation’s solution using a mini spray drier. A rigorous assessment was conducted on particle size distribution, structural thermal analysis, morphology study, in vitro silico investigation, counter addition the solubility, dissolution, diffusion of TN. Results: containing leucine glycine revealed superior characteristics (mass median diameter (MMAD): 4.6–5 µm, fraction (FPF): 30.6–35.1%, amorphous spherical structure) as candidates further development TN-DPIs, while arginine excluded due intensive aggregation hygroscopicity, which led poor performance. TN samples demonstrated micronized particles (D [0.5]: 3.99–5.96 µm) with predominantly structure (crystallinity index: 24.1–45.2%) significant solubility enhancement (~19-fold). Formulations leucine-glycine highest FPF (45.7–47.8%) deposition (39.3–40.1%), rapid drug release (~100% within 10 min), improved (2.29–2.43-fold), respectively. Moreover, confirmed microparticles (mean number = 2.3–2.02 µm). Conclusions: This innovative formulation possesses enhanced physicochemical, morphological, low-dose local treatment could be applied promising carrier dry inhaler

Язык: Английский

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Integrated transcriptomics and network pharmacology to reveal the mechanism of Physochlainae Radix in the treatment of asthma

Phytomedicine, Год журнала: 2025, Номер 139, С. 156470 - 156470

Опубликована: Фев. 6, 2025

Язык: Английский

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Innovative approaches to asthma treatment: harnessing nanoparticle technology

Discover Nano, Год журнала: 2025, Номер 20(1)

Опубликована: Фев. 8, 2025

In the domain of respiratory illnesses, asthma remains a critical obstacle. The heterogeneous nature this chronic inflammatory disease poses challenges during its treatment. Glucocorticoid-based combination drug therapy now dominates clinical treatments for asthma; however, glucocorticoid resistance, numerous adverse effects, incidence inadequate delivery, and other factors need development more effective therapies. recent years, there has been extensive research on nanotechnology in medicine. It shown studies that these delivery systems can greatly enhance targeting bioavailability decrease toxicity medication. Nanoparticle offer improved therapeutic efficacy compared to conventional administration techniques. Nanotechnology enables advancements precision medicine, offering benefits conditions such as asthma. This review will examine consider when formulating medications, well role nanomaterials their mechanisms action pulmonary medicine

Язык: Английский

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AAV-mediated MUC5AC siRNA delivery to prevent mucociliary dysfunction in asthma

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

The main structural components of mucus produced in the lung are mucin 5B (MUC5B) and 5AC (MUC5AC) where a relatively higher expression MUC5B is typical health. In lungs individuals with asthma, there shift from to MUC5AC as predominantly secreted which has been shown impair mucociliary clearance (MCC) increase plug formation airways. Given its role asthmatic disease, represents potential therapeutic target gene delivery approach could be leveraged modulate expression. For these purposes, we explored adeno-associated virus serotype 6 (AAV6), lung-tropic viral vector airway epithelial cells reduce via siRNA delivery. We confirmed that AAV6 was able transduce airways healthy mice high transgene mucus-secreting goblet cells. Using multiple particle tracking analysis, observed capable penetrating both normal MUC5AC-enriched barriers. Successful transduction also achieved IL-13 stimulated human (HAE) differentiated at air-liquid interface (ALI). expressing MUC5AC-targeting evaluated prophylactic treatment HAE cell cultures before challenge. treated AAV6-MUC5AC had significantly reduced mRNA protein compared untreated controls. Mucociliary transport maintained comparable controls following treatment. Together, findings support may used an inhaled therapy suppress overexpression restore function asthma.

Язык: Английский

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Allergy Treatment: A Comprehensive Review of Nanoparticle-based Allergen Immunotherapy

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(3)

Опубликована: Март 20, 2025

Allergic disorders rising in prevalence globally, affecting a substantial proportion of individuals industrialized nations. The imbalance the immune system, characterized by elevated allergen-specific T helper 2 (Th2) cells and immunoglobulin E (IgE) antibodies, is key factor allergy development. Allergen-specific immunotherapy (AIT) only treatment capable alleviating allergic symptoms, preventing new sensitizations, reducing asthma risk rhinitis patients. Traditional AIT, however, faces challenges such as frequent administration, adverse effects, inconsistent patient outcomes. Nanoparticle-based approaches have emerged promising strategy to enhance AIT. This review explores utilization nanoparticles highlighting their ability interact with system improve therapeutic Various types nanoparticles, including polyesters, polysaccharide polymers, liposomes, protamine-based (NPs), polyanhydrides, been employed adjuvants or carriers AIT’s efficacy safety. Nanoparticles offer advantages allergen protection, improved response modulation, targeted cell delivery, reduced side effects. provides an overview current landscape nanoparticle-based immunotherapy, discussing its potential revolutionize compared traditional immunotherapy.

Язык: Английский

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Targeted Drug Delivery System for Pulmonary Fibrosis: Design and Development of Biomaterials

BIO Integration, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 1, 2025

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive extracellular matrix deposition and tissue scarring, leading to impaired function respiratory failure. Although current treatments, such as pirfenidone nintedanib, slow progression, they fail completely halt or reverse fibrosis. Therefore, innovative therapeutic strategies are needed. Targeted drug delivery systems (TDDSs) emerging promising solutions. Biomaterials play critical roles in these enhancing specificity, availability, efficacy, while minimizing systemic toxicity. The most notable biomaterials include nanotechnology-based systems, including liposomes polymeric nanoparticles, which facilitate penetration release fibrotic tissues. Hydrogels have three-dimensional structures providing controlled sustained at inflammation sites, therefore particularly valuable PF treatment. Furthermore, biological carriers stem cells vesicles biocompatibility anti-inflammatory effects that improve outcomes. Despite the potential of clinical translation hindered several challenges, immune clearance, stability platforms, optimization retention within diseased Interdisciplinary approaches integrating precision medicine with advancements may provide solutions opening new avenues for This review discusses developments targeted PF, emphasizing importance biomaterials, mechanisms barriers involved pulmonary delivery, future perspectives overcoming limitations. ultimate goal patient outcomes revolutionizing approach treatment through advanced technologies.

Язык: Английский

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Clinical Translation Challenges and Strategies for Tumour Vaccines Considering Multiple Delivery Routes

Vaccines, Год журнала: 2025, Номер 13(5), С. 469 - 469

Опубликована: Апрель 27, 2025

Background: The high incidence and mortality rates of cancer have kept it at the top research agenda for global healthcare industry, as well put serious economic pressure on families society. It has gradually been recognised that reducing through various interventions combining prevention treatment are key to alleviating burden cancer. Methods: Retrieve summarize literature related delivery methods tumor vaccines, investigate whether these applied clinically or used in clinical trials. Results: there a variety vaccine development, but only very small number studies able make strides towards implementing clinic, which is closely linked drawbacks with means delivery. Conclusions: This review analyses reasons why difficult apply clinic from point view method rather than design vaccine. also describes some not yet vaccines and, considering this conjunction those currently purpose, predicts their prospects future application.

Язык: Английский

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LungVis 1.0: an automatic AI-powered 3D imaging ecosystem unveils spatial profiling of nanoparticle delivery and acinar migration of lung macrophages

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 27, 2024

Abstract Targeted (nano-)drug delivery is essential for treating respiratory diseases, which are often confined to distinct lung regions. However, spatio-temporal profiling of drugs or nanoparticles (NPs) and their interactions with macrophages remains unresolved. Here, we present LungVis 1.0, an AI-powered imaging ecosystem that integrates light sheet fluorescence microscopy deep learning-based image analysis pipelines map NP deposition dosage holistically quantitatively across bronchial alveolar (acinar) regions in murine lungs widely-used bulk-liquid aerosol-based methods. We demonstrate results patchy distribution elevated doses, whereas aerosols achieve uniform reaching distal alveoli. Furthermore, reveal tissue-resident (TRMs) dynamic, actively patrolling redistributing NPs within alveoli, contesting the conventional paradigm TRMs as static entities. 1.0 provides advanced framework exploring pulmonary dynamics deepening insights into TRM-mediated immunity.

Язык: Английский

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Site-specific inhibition of neutrophilic inflammation by low-dose nanotherapy for immunoregulatory treatment of asthma

Nano Today, Год журнала: 2023, Номер 52, С. 101957 - 101957

Опубликована: Авг. 14, 2023

Язык: Английский

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