Optimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA

Hao, Miao; Li, Yingwen; Li, Renjie; Zhou, Xudong; Shi, Jingyu; Tong, Zhenbo; Sun, Zhenhua; Yu, Aibing

doi:10.1016/j.ijpharm.2023.123050

Cited by 22 publications

(8 citation statements)

References 51 publications

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“…Miao et al also reported using LNPs to prepare soft mist inhaler (SMI) for encapsulated mRNA pulmonary delivery. [118] The investigation found that a trehaloseincorporated buffer system could improve the entrapment efficiency and particle size of LNPs, providing a successful example of their application in aqueous formulation pulmonary delivery of nucleic acid.…”

Section: Saccharidesmentioning

confidence: 99%

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency

Wang,

Bu,

Dai

et al. 2024

Advanced Science

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Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.

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Section: Saccharidesmentioning

confidence: 99%

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency

Wang,

Bu,

Dai

et al. 2024

Advanced Science

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“…The prerequisite for liposome pulmonary delivery is to convert the liposome system into an inhalation preparation for clinical use. As for the inhalers adapted for the inhalation preparations, nebulizers [ 33 ], Dry Powder Inhalers (DPIs) [ 34 ], Soft Mist Inhalers (SMIs) [ 35 ], and pressurized metered-dose inhalers (pMDIs) [ 36 ] can be selected. The adaptability of these inhalers with liposomes for inhalation is scrutinized below.…”

Section: Pressurized Metered-dose Inhalers Are Promising For Liposome...mentioning

confidence: 99%

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization

Huang,

Chang,

Gao

et al. 2024

IJMS

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Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

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“…LNPs have potential as carriers for mRNA vaccines in tumor therapy, but there are still some challenges that need to be overcome to achieve their widespread application [ 249 ]. One of the challenges is the stability and immunogenicity of LNPs in vivo [ 250 , 251 , 252 ]. LNPs may suffer from protein adsorption and micellar rupture in blood circulation, limiting their ability to effectively deliver mRNA vaccines.…”

Section: Future Prospects and Challengesmentioning

confidence: 99%

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

Wu,

Li,

Qian

et al. 2024

Vaccines

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In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells in cancer therapy has become a strategy of great research interest. mRNA vaccines are a potential choice for tumor immunotherapy, due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery carrier, and their structural stability and biocompatibility make them an effective means for delivering mRNA to specific targets. This study summarizes the research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity, and targeting is discussed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy, as well as to provide more effective treatment plans for patients.

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Optimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA

Cited by 22 publications

References 51 publications

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

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