Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics

Leong, Ellenmae W. X.; Ge, Ruowen

doi:10.3390/biomedicines10092179

Cited by 60 publications

(37 citation statements)

References 151 publications

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“…In comparison, this fraction is greater than that of Arikayce (FPF 5μm : 50.3%-53.5%), the only clinically approved liposomal drug developed for inhalation. 60,61 Compared to Arikayce, the MMAD is also <5 μm for all LNPs except A-1. In addition, the GSD was also less than 2 for all LNPs.…”

Section: Characterization Of Lnp Morphology Before and After Aerosoli...mentioning

confidence: 88%

Optimization of ionizable lipids for aerosolizable mRNA lipid nanoparticles

Lewis,

Soto,

Maier

et al. 2023

Bioengineering & Transla Med

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Although mRNA lipid nanoparticles (LNPs) are highly effective as vaccines, their efficacy for pulmonary delivery has not yet fully been established. A major barrier to this therapeutic goal is their instability during aerosolization for local delivery. This imparts a shear force that degrades the mRNA cargo and therefore reduces cell transfection. In addition to remaining stable upon aerosolization, mRNA LNPs must also possess the aerodynamic properties to achieve deposition in clinically relevant areas of the lungs. We addressed these challenges by formulating mRNA LNPs with SM‐102, the clinically approved ionizable lipid in the Spikevax COVID‐19 vaccine. Our lead candidate, B‐1, had the highest mRNA expression in both a physiologically relevant air–liquid interface (ALI) human lung cell model and in healthy mice lungs upon aerosolization. Further, B‐1 showed selective transfection in vivo of lung epithelial cells compared to immune cells and endothelial cells. These results show that the formulation can target therapeutically relevant cells in pulmonary diseases such as cystic fibrosis. Morphological studies of B‐1 revealed differences in the surface structure compared to LNPs with lower transfection efficiency. Importantly, the formulation maintained critical aerodynamic properties in simulated human airways upon next generation impaction. Finally, structure–function analysis of SM‐102 revealed that small changes in the number of carbons can improve upon mRNA delivery in ALI human lung cells. Overall, our study expands the application of SM‐102 and its analogs to aerosolized pulmonary delivery and identifies a potent lead candidate for future therapeutically active mRNA therapies.

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Section: Characterization Of Lnp Morphology Before and After Aerosoli...mentioning

confidence: 88%

Optimization of ionizable lipids for aerosolizable mRNA lipid nanoparticles

Lewis,

Soto,

Maier

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…99 Lipid nanoparticles (LNPs) are lipid vesicles with a homogeneous lipid core. 100 LNPs include ionizable and cationic lipids, cholesterol, phospholipids, and PEG lipids, of which ionizable lipids play an important role in protecting nucleic acids from nuclease-mediated degradation. The encapsulated drugs are distributed within the hydrophobic layer, hydrophilic cavity, or on the surface of the nanoparticles.…”

Section: Liposomes and Their Derivativesmentioning

confidence: 99%

Biomaterial‐based gene therapy

Gao

et al. 2023

MedComm

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Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial‐based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial‐based gene delivery systems. Furthermore, the current applications of biomaterial‐based gene therapy are summarized.

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“…Third, the small size of LNPs allows them to reach deep lung tissues, which is often necessary for effective treatment. Finally, LNPs can adhere to the mucosal surface, extending residency time in lung tissue and improving pharmacokinetic profiles 2 .…”

Section: Nature Biotechnologymentioning

confidence: 99%

“…These cells secrete mucus and other factors into the lumen, which, together with oscillating cilia, efficiently entrap and clear foreign particles. Additionally, alveolar macrophages internalize and clear foreign particles and pathogens that enter the airway 2 .…”

mentioning

confidence: 99%