Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development - PubMed (original) (raw)

Review

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

Meenu Mehta et al. ACS Mater Au. 2023.

Abstract

Over the past decade, the therapeutic potential of nanomaterials as novel drug delivery systems complementing conventional pharmacology has been widely acknowledged. Among these nanomaterials, lipid-based nanoparticles (LNPs) have shown remarkable pharmacological performance and promising therapeutic outcomes, thus gaining substantial interest in preclinical and clinical research. In this review, we introduce the main types of LNPs used in drug formulations such as liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and lipid polymer hybrid nanoparticles, focusing on their main physicochemical properties and therapeutic potential. We discuss computational studies and modeling techniques to enhance the understanding of how LNPs interact with therapeutic cargo and to predict the potential effectiveness of such interactions in therapeutic applications. We also analyze the benefits and drawbacks of various LNP production techniques such as nanoprecipitation, emulsification, evaporation, thin film hydration, microfluidic-based methods, and an impingement jet mixer. Additionally, we discuss the major challenges associated with industrial development, including stability and sterilization, storage, regulatory compliance, reproducibility, and quality control. Overcoming these challenges and facilitating regulatory compliance represent the key steps toward LNP's successful commercialization and translation into clinical settings.

© 2023 The Authors. Published by American Chemical Society.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1

Figure 1

Chemical structures of various components used in LNP formulations. These include phospholipids (1,2-dioleoyl-_sn_-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-_sn_-glycero-3-phosphocholine (DOPC), and phosphatidylinositol), cholesterol, cationic and ionizable lipids (1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), (1,2-dilinoleyloxy-3-dimethylaminopropane) (Dlin-MC3-DMA)), and PEG lipids (1,2-distearoyl-_sn_-glycero-3-phosphoethanolamine-_N_-[methoxy(polyethylene glycol)](DSPE-PEG), 1,2-distearoyl-_sn_-glycero-3-phosphoethanolamine-_N_-[succinyl(polyethylene glycol)] (DSG-PEG)).

Figure 2

Figure 2

Schematic illustration depicts the structure of various LNP formulations used in drug delivery. (A) Liposomes are spherical vesicles with phospholipid bilayers, encapsulating hydrophilic drugs in their aqueous core and incorporating hydrophobic drugs within the lipid bilayers. (B) Nanoemulsions comprise oil droplets dispersed in an aqueous phase stabilized by surfactants, accommodating lipophilic drugs in the oil phase while preventing droplet aggregation. (C) Solid lipid nanoparticles (SLNs) consist of solid lipid matrices entrapping hydrophobic drugs, forming nanoscale particles with a lipid core. (D) Nanostructured lipid carriers (NLCs) are similar to SLNs but contain a combination of solid and liquid lipids, resulting in a more stable matrix and improved drug loading capacity. (E) Lipid polymer hybrid nanoparticles combine lipid-based and polymer-based components, offering the benefits of both systems. These nanoparticles can effectively encapsulate various types of drugs and exhibit enhanced stability and controlled release properties. Each type of LNP structure provides unique advantages and can be tailored for targeted drug delivery, enabling the encapsulation of a diverse range of therapeutic agents. Figure created with

BioRender.com

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Figure 3

Figure 3

LNP synthesis processes in laboratory and industry environments: (A) Nanoprecipitation, (B) single/double emulsification, (C) nonsolvent emulsification, (D) thin film hydration, (E) microfluidic process, and (F) impingement jet mixer. Created with

BioRender.com

.

Figure 4

Figure 4

Different designs of microchips used in microfluidic devices: (A) Y-shaped mixer, (B) hydrodynamic flow focusing, (C) staggered herringbone mixer, and (D) bifurcating mixer. Created with

BioRender.com

.

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