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Review
. 2024 Mar 13;25(6):3261.
doi: 10.3390/ijms25063261.

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

Yeqi Huang  1 , Ziyao Chang  2 , Yue Gao  1 , Chuanyu Ren  1 , Yuxin Lin  1 , Xuejuan Zhang  1 , Chuanbin Wu  1 , Xin Pan  2 , Zhengwei Huang  1
Affiliations
Review

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

Yeqi Huang et al. Int J Mol Sci. .

Abstract

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.

Keywords: biomimetic materials; biomineralization; clinical translation; liposome; metered-dose inhalers; shell structure.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 5
Figure 5
(A) Adsorption of charged liposomal formulations to HA. Reproduced from [125]. Copyright 2010, Elsevier. (B) SEM micrographs of vaterite precipitated after 10 min of aging time in the (a) absence and presence of different liposomes: EPC (b), DMPC (c), and DMPS (d,e). Reproduced from [126]. (C) Affinity of BPA-liposomes to HA. Reproduced from [127]. Copyright 2009, Elsevier. (D) (a) A gas diffusion method, (b) the types and sizes of crystals obtained in each microwell as a function of lecithin concentration. Reproduced from [128]. Copyright 2015, Royal Society of Chemistry. (E) Schematic of the construction of Sal@CaCO3/A23187 for enhanced immunotherapy. Reproduced from [134].
Figure 7
Figure 7
(A) Schematic depiction of the synthesis and biomineralization of PPL nanogels. Reproduced from [182]. Copyright: 2019, John Wiley and Sons. (B) SEM images: (a) Bare S. cerevisiae; (b) S. cerevisiae cells are hardly calcified and calcium minerals precipitate separately; (c) some calcium minerals precipitate randomly on the bare cell; (d) S. cerevisiae with a mineral coat after the LbL treatment. Reproduced from [193]. Copyright: 2008, John Wiley and Sons. (C) Schematic representation of controlling mineralization over the surface of nanocapsules by tuning the rate and direction of ion diffusion, surface functional groups, and the reaction conditions Reproduced from [124]. (D) Schematic of the formation and stability mechanisms of FL Lipo-C-P. Reproduced from [194]. Copyright: 2023, Elsevier.
Figure 1
Figure 1
Illustration of liposome nano architectonics.
Figure 2
Figure 2
Illustration of pMDI structure.
Figure 3
Figure 3
(A) Propellant medium-induced low stability of liposomal pMDI; (B) Mechanical stress-induced low stability of liposomal pMDI; (C) Physical barrier strategy; (D) Reason for failure of physical barrier strategy in propellant medium; (E) Shell stabilization strategy.
Figure 4
Figure 4
Biomineralization in biomedical applications.
Figure 6
Figure 6
(A) Schematic representations of silica encapsulation in a liquid liposome and FIB-SEM images of SLPs. Reproduced from [142]. Copyright: 2021, American Chemical Society. (B) Schematic representations of silica sol generation. By varying the buffer ionic constituents, concentration, pH, and sol aging temperature, the silica particle size in silica sols can be controlled. Reproduced from [145]. Copyright: 2017, American Chemical Society (C) TEM image of helical silica. Reproduced from [146]. Copyright: 2009, American Chemical Society. (D) Effect of Triton X-100 on the physical stability of PTX liposomes and liposils with respect to (a) particle size, (b) polydispersity index (PDI), (c) entrapment efficiency (**** p < 0.0001), and the corresponding effect seen from the (d) in vitro release profile of PTX from Taxol® (A commercial PTX product.), PTX liposomes, and PTX liposils over a period of 72 h. Reproduced from [147]. Copyright: 2018, Elsevier B.V. (E) a. Scheme of manganese dioxide-coated liposomes. b. In vivo T1-weighted MRI imagesof a Lipo/HMME/ACF@MnO2, and b Lipo/HMME/ACF@MnO2-AS1411. Reproduced from [148]. Copyright: 2018, John Wiley and Sons. (F) Illustration of liposome@Gd3+/AMP. Reproduced from [149]. Copyright: 2019, American Chemical Society.
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References

    1. Couvreur P. Nanoparticles in drug delivery: Past, present and future. Adv. Drug Deliv. Rev. 2013;65:21–23. doi: 10.1016/j.addr.2012.04.010. - DOI - PubMed
    1. Song Y., Peng C., Iqbal Z., Sirkar K.K., Peterson G.W., Mahle J.J., Buchanan J.H. Graphene Oxide and Metal-Organic Framework-Based Breathable Barrier Membranes for Toxic Vapors. ACS Appl. Mater. Interfaces. 2022;14:31321–31331. doi: 10.1021/acsami.2c07989. - DOI - PubMed
    1. Kinnear C., Moore T.L., Rodriguez-Lorenzo L., Rothen-Rutishauser B., Petri-Fink A. Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine. Chem. Rev. 2017;117:11476–11521. doi: 10.1021/acs.chemrev.7b00194. - DOI - PubMed
    1. Hussein A.K. Applications of nanotechnology to improve the performance of solar collectors—Recent advances and overview. Renew. Sustain. Energy Rev. 2016;62:767–792. doi: 10.1016/j.rser.2016.04.050. - DOI
    1. Yan M., Chen Q., Liu T., Li X., Pei P., Zhou L., Zhou S., Zhang R., Liang K., Dong J., et al. Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma. Nat. Commun. 2023;14:4628. doi: 10.1038/s41467-023-40300-2. - DOI - PMC - PubMed

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