Small-angle X-ray and neutron scattering applied to lipid-based nanoparticles: Recent advancements across different length scales

Advances in Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 327, P. 103156 - 103156

Published: April 12, 2024

Lipid-based nanoparticles (LNPs), ranging from nanovesicles to non-lamellar assemblies, have gained significant attention in recent years, as versatile carriers for delivering drugs, vaccines, and nutrients. Small-angle scattering methods, employing X-rays (SAXS) or neutrons (SANS), represent unique tools unveil structure, dynamics, interactions of such particles on different length scales, spanning the nano molecular scale. This review explores state-of-the-art methods applied structure lipid-based their with drugs bioactive molecules, inform rational design formulation medical applications. We will focus complementary information accessible neutrons, insights colloidal processes at a nanoscale level details lipid organization LNPs (SANS). In addition, we new opportunities offered by Time-resolved (TR)-SAXS -SANS investigation dynamic involving LNPs. These span real-time monitoring structural evolution response endogenous external stimuli (TR-SANS), kinetics diffusion exchange upon interaction biomolecules (TR-SANS). Finally, spotlight novel combinations SAXS SANS on-line techniques, recently enabled Large Scale Facilities neutrons. emerging technology enables synchronized multi-method investigation, offering exciting simultaneous characterization chemical mechanical properties

Language: Английский

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Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

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Neutron reflectometry as a powerful tool to elucidate membrane interactions of drug delivery systems

Advances in Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 325, P. 103120 - 103120

Published: Feb. 28, 2024

The last couple of decades have seen an explosion novel colloidal drug delivery systems, which been demonstrated to increase efficacy, reduce side-effects, and provide various other advantages for both small-molecule biomacromolecular drugs. interactions systems with biomembranes are increasingly recognized play a key role efficient eradication pathogens cancer cells, as well intracellular protein nucleic acid In parallel, there has broadening methodologies investigating such systems. For example, advanced microscopy, mass-spectroscopic "omic"-techniques, small-angle X-ray neutron scattering techniques, only few years ago were largely restricted rather specialized areas within basic research, currently seeing increased interest from researchers wide application fields. the present discussion, focus is placed on use reflectometry investigate membrane Although technique still less extensively employed investigations than, e.g., scattering, studies may mechanistic information regarding binding, re-modelling, translocation, permeation, importance efficacy toxicity antimicrobial, cancer, therapeutics. following, examples this discussed gaps/opportunities in research field identified.

Language: Английский

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Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery

International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 8, P. 100283 - 100283

Published: Sept. 10, 2024

Language: Английский

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Toward understanding lipid reorganization in RNA lipid nanoparticles in acidic environments

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(45)

Published: Oct. 30, 2024

The use of lipid nanoparticles (LNPs) for therapeutic RNA delivery has gained significant interest, particularly highlighted by recent milestones such as the approval Onpattro and two mRNA-based SARS-CoV-2 vaccines. However, despite substantial advancements in this field, our understanding structure internal organization RNA-LNPs -and their relationship to efficacy, both vitro vivo- remains limited. In study, we present a coarse-grained molecular dynamics (MD) approach that allows simulations full-size LNPs. By analyzing MD-derived structural characteristics conjunction with cellular experiments, investigate effect critical parameters, pH composition, on LNP potency. Additionally, examine mobility chemical environment within LNPs at level. Our findings highlight impact composition can have key stages LNP-based intracellular delivery.

Language: Английский

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Advancement in lipid-based nanocomposites for theranostic applications in lung carcinoma treatment

OpenNano, Journal Year: 2023, Volume and Issue: 15, P. 100199 - 100199

Published: Dec. 25, 2023

On a global scale, lung cancer remains common malignancy and is largest cause of many deaths related to cancer. Despite the significant advancements in diagnostic therapeutic approaches, individuals exhibit resistant responses proven therapies. This focuses on critical need for novel methods be developed innovated. Recently, nanotechnology has gained lot importance treating as it helps improve drug delivery, specificity, reduced dose, efficient elimination. Lipid nanoparticles (LNPs) are nanocarriers with low particle size, which can modified specific delivery. The current review significance application lipid-based theranostic therapy, components, method preparation factors affecting lipid nanoparticle preparation, along clinical trials patents LNPs. Therapeutic applications therapy include Chemotherapy, photodynamic immunotherapy, gene photothermal sonodynamic therapy. Diagnostic like SPECT, CT, MRI, PET, Optical fluorescence imaging NIR. As LNPs being used more frequently ongoing research offering solutions overcome issues by conventional treatments. Due their adaptability customized medical procedures use numerous they hold potential In conclusion, offer viable strategy boosting bioavailability, promoting medication removing obstacles. For individualised medicine, encapsulate range therapeutic, such immunomodulatory medicines, siRNA, chemotherapeutic medications. Additional study validation required address scalability, long-term safety, optimised manufacturing techniques effective

Language: Английский

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Technologies for Targeted RNA Degradation and Induced RNA Decay

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

The vast majority of the human genome codes for RNA, but RNA-targeting therapeutics account a small fraction approved drugs. As such, there is great incentive to improve old and develop new approaches RNA targeting. For many targeting modalities, just binding not sufficient exert therapeutic effect; thus, targeted degradation induced decay emerged as powerful with pronounced biological effect. This review covers origins advanced use cases degrader technologies grouped by nature modality well mode degradation. It both well-established methods clinically successful platforms such interference, emerging recruitment quality control machinery, CRISPR, direct We also share our thoughts on biggest hurdles in this field, possible ways overcome them.

Language: Английский

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Unravelling the interactions between small molecules and liposomal bilayers via molecular dynamics and thermodynamic modelling

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 660, P. 124367 - 124367

Published: June 18, 2024

Lipid-based drug delivery systems hold immense promise in addressing critical medical needs, from cancer and neurodegenerative diseases to infectious diseases. By encapsulating active pharmaceutical ingredients - ranging small molecule drugs proteins nucleic acids these nanocarriers enhance treatment efficacy safety. However, their commercial success faces hurdles, such as the lack of a systematic design approach issues related scalability reproducibility. This work aims provide insights into drug-phospholipid interaction by combining molecular dynamic simulations thermodynamic modelling techniques. In particular, we have made connection between structural properties system physicochemical performance drug-loaded liposomal nanoformulations. We considered two prototypical drugs, felodipine (FEL) naproxen (NPX), one model hydrogenated soy phosphatidylcholine (HSPC) bilayer membrane. Molecular revealed which regions within phospholipid bilayers are most least favoured molecules. NPX tends reside at water-phospholipid interface is characterized lower free energy barrier for membrane permeation. Meanwhile, FEL prefers sit hydrophobic tails phospholipids higher Flory-Huggins modelling, angle X-ray scattering, light TEM, release studies nanoformulations confirmed this difference. The naproxen-phospholipid has permeation, miscibility with bilayer, larger nanoparticle size, faster aqueous medium than felodipine. suggest that combination dynamics thermodynamics may offer new tool designing developing lipid-based unmet applications.

Language: Английский

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Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115461 - 115461

Published: Oct. 1, 2024

Language: Английский

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Real‐Time pH‐Dependent Self‐Assembly of Ionisable Lipids from COVID‐19 Vaccines and In Situ Nucleic Acid Complexation

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(35)

Published: July 1, 2023

Abstract Ionisable amino‐lipid is a key component in lipid nanoparticles (LNPs), which plays crucial role the encapsulation of RNA molecules, allowing efficient cellular uptake and then releasing from acidic endosomes. Herein, we present direct evidence for remarkable structural transitions, with decreasing membrane curvature, including inverse micellar, to hexagonal, two distinct bicontinuous cubic, finally lamellar phase mainstream COVID‐19 vaccine ionisable ALC‐0315 SM‐102 lipids, occurring upon gradual acidification as encountered The millisecond kinetic growth cubic hexagonal structures evolution ordered formation lipid‐RNA/DNA complexation are quantitatively revealed by situ synchrotron radiation time‐resolved small angle X‐ray scattering coupled rapid flow mixing. We found that final self‐assembled identity, kinetics, were controlled molecular structure, bulk environment, compositions, nucleic acid structure/size. implicated link between curvature LNP endosomal escape helps future optimisation lipids engineering gene delivery.

Language: Английский

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