The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles DOI Creative Commons

Ramon González-Rioja,

Vivian A. Salazar, Neus G. Bastús

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 27, 2023

The long quest for efficient drug administration has been looking a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main delivery dilemmas. On one side, versatility of vehicle efficiently load, protect then release it at target place. other hand, questions related degree PEGylation which are needed avoid nanoparticle (NP) aggregation opsonization while preventing cellular uptake. development different kinds lipidic vehicles particles resulted in ionizable lipid nanoparticles (iLNPs), most typical problems. Proof their success is late approval massive as prophylactic vaccine SARS-CoV-2. These ILNPs built by electrostatic surfactants, agent, lipids self-segregate from an aqueous solution, forming stabilized with polymers, such PEG. previous limitations low loading high toxicity, likely thanks charge working pH reduced size, entry into cells via endocytosis rather than membrane perforation or fusion, always associated higher toxicity. We herein revise primary features, synthetic methods prepare characterize them, pharmacokinetic (administration, distribution, metabolization excretion) aspects, biodistribution fate. Owing advantages, iLNPs potential systems improve management various diseases widely available clinical use.

Язык: Английский

A highly efficient needle-free-injection delivery system for mRNA-LNP vaccination against SARS-CoV-2 DOI Creative Commons

Shanhong Mao,

Shiyou Li, Yuxin Zhang

и другие.

Nano Today, Год журнала: 2022, Номер 48, С. 101730 - 101730

Опубликована: Дек. 21, 2022

Despite the various vaccines that have been developed to combat coronavirus disease 2019 (COVID-19) pandemic, persistent and unpredictable mutations of severe acute respiratory syndrome 2 (SARS-CoV-2) require innovative unremitting solutions cope with resultant immune evasion establish a sustainable barrier. Here we introduce vaccine-delivery system combination needle-free injection (NFI) device SARS-CoV-2-Spike-specific mRNA-Lipid Nanoparticle (LNP) vaccine. The benefits are duller pain significant increase immunogenicity compared canonical needle (NI). From physicochemical bioactivity analyses, structure mRNA-LNP maintains stability upon NFI, contradictory belief LNPs inclined towards destruction under high-pressure conditions NFI. Moreover, vaccine delivered by NFI induces significantly more binding neutralizing antibodies against SARS-CoV-2 variants than same NI. Heterogeneous vaccination BA.5-LNP enhanced generation Omicron BA.5 in rabbits previously vaccinated non-BA.5-specific or other COVID-19 vaccines. parameters can be adjusted deliver subcutaneously intramuscularly. Taken together, our results suggest NFI-based is an effective substitute for traditional NI-based vaccination.

Язык: Английский

Процитировано

32
Modeling human immune responses to vaccination in vitro DOI
Elena Morrocchi, Simon D. van Haren, Paolo Palma

и другие.

Trends in Immunology, Год журнала: 2023, Номер 45(1), С. 32 - 47

Опубликована: Дек. 21, 2023

Язык: Английский

Процитировано

19
3D printed tissue models: From hydrogels to biomedical applications DOI Creative Commons
Francesca Cadamuro, Francesco Nicotra, Laura Russo

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 354, С. 726 - 745

Опубликована: Янв. 26, 2023

The development of new advanced constructs resembling structural and functional properties human organs tissues requires a deep knowledge the morphological biochemical extracellular matrices (ECM), capacity to reproduce them. Manufacturing technologies like 3D printing bioprinting represent valuable tools for this purpose. This review will describe how ECM change in different tissues, organs, healthy pathological states, mimics with required can be generated by bioprinting. describes classifies polymeric materials natural synthetic origin exploited generate hydrogels acting as "inks" process, particular emphasis on their functionalization allowing crosslinking conjugation signaling molecules develop bio-responsive bio-instructive mimics.

Язык: Английский

Процитировано

18
Bridging the Gap: Integrating 3D Bioprinting and Microfluidics for Advanced Multi-Organ Models in Biomedical Research DOI Creative Commons
Marco De Spirito, Valentina Palmieri, Giordano Perini

и другие.

Bioengineering, Год журнала: 2024, Номер 11(7), С. 664 - 664

Опубликована: Июнь 28, 2024

Recent advancements in 3D bioprinting and microfluidic lab-on-chip systems offer promising solutions to the limitations of traditional animal models biomedical research. Three-dimensional enables creation complex, patient-specific tissue that mimic human physiology more accurately than models. These bioprinted tissues, when integrated with systems, can replicate dynamic environment body, allowing for development multi-organ This integration facilitates precise drug screening personalized therapy by simulating interactions between different organ systems. Such innovations not only improve predictive accuracy but also address ethical concerns associated testing, aligning three Rs principle. Future directions include enhancing resolution, developing advanced bioinks, incorporating AI optimized system design. technologies hold potential revolutionize development, regenerative medicine, disease modeling, leading effective, personalized, humane treatments.

Язык: Английский

Процитировано

9
Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach DOI Creative Commons

Ehsan Bitaraf Haghighi,

Samira Sadat Abolmaali, Ali Dehshahri

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 14, 2024

RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects

Язык: Английский

Процитировано

8
Efficient Delivery of DNA Using Lipid Nanoparticles DOI Creative Commons
Lishan Cui, Serena Renzi, Erica Quagliarini

и другие.

Pharmaceutics, Год журнала: 2022, Номер 14(8), С. 1698 - 1698

Опубликована: Авг. 15, 2022

DNA vaccination has been extensively studied as a promising strategy for tumor treatment. Despite the efforts, therapeutic efficacy of vaccines limited by their intrinsic poor cellular internalization. Electroporation, which is based on application controlled electric field to enhance penetration into cells, method choice produce acceptable levels gene transfer in vivo. However, this may cause cell damage or rupture, non-specific targeting, and even degradation pDNA. Skin irritation, muscle contractions, pain, alterations skin structure, irreversible have frequently reported. To overcome these limitations, work, we use microfluidic platform generate DNA-loaded lipid nanoparticles (LNPs) are then characterized combination dynamic light scattering (DLS), synchrotron small-angle X-ray (SAXS), transmission electron microscopy (TEM). clinical successes obtained LNPs mRNA siRNA delivery, little known about encapsulating bulkier molecules, remains challenging. For vitro screening, were administered human embryonic kidney 293 (HEK-293) Chinese hamster ovary (CHO) lines ranked transfection efficiency (TE) cytotoxicity. The LNP formulation exhibiting highest TE lowest cytotoxicity was tested delivery vaccine pVAX-hECTM targeting neoantigen HER2, an oncoprotein overexpressed several cancer types. Using fluorescence-activated sorting (FACS), immunofluorescence assays fluorescence confocal (FCS), proved that pVAX-hECTM-loaded massive expression HER2 antigen membrane HEK-293 cells. Our results provide new insights structure-activity relationship pave way access technology preclinical studies.

Язык: Английский

Процитировано

28
Microfluidic-based technologies for diagnosis, prevention, and treatment of COVID-19: recent advances and future directions DOI Open Access
E. Alperay Tarim, Müge Anıl-İnevi,

Ilayda Ozkan

и другие.

Biomedical Microdevices, Год журнала: 2023, Номер 25(2)

Опубликована: Март 13, 2023

Язык: Английский

Процитировано

16
Why mRNA-ionizable LNPs formulations are so short-lived: causes and way-out DOI
Anindita De, Young Tag Ko

Expert Opinion on Drug Delivery, Год журнала: 2023, Номер 20(2), С. 175 - 187

Опубликована: Янв. 1, 2023

Introduction Messenger ribonucleic acid (mRNA) and small interfering RNA (siRNA) are biological molecules that can be heated, frozen, lyophilized, precipitated, or re-suspended without degradation. Currently, ionizable lipid nanoparticles (LNPs) a promising approach for mRNA therapy. However, the long-term shelf-life stability of mRNA–ionizable LNPs is one open questions about their use safety. At an acidic pH, lipids shield anionic mRNA. under storage conditions remains mystery. Moreover, excipients also cause instability during storage.Area covered This paper aims to illustrate why mRNA-ionizable have such limited half-life. For first time, we compile tentative reasons short half-life ultra-cold mRNA-LNPs in context formulation excipients. The article provided possible ways prolonging lifespan long storage.Expert opinion future genetic medicine. Current limitations overcome by advanced drying process whole new hybrid strategy extend shelf life LNPs. A breakthrough technology may up research directions producing thermostable safe at room temperature.

Язык: Английский

Процитировано

15
PEG vs. zwitterions: How these surface decorations determine cellular uptake of lipid-based nanocarriers DOI Creative Commons
Daniel Stengel,

Betül Hilal Demirel,

Patrick Knoll

и другие.

Journal of Colloid and Interface Science, Год журнала: 2023, Номер 647, С. 52 - 64

Опубликована: Май 18, 2023

To evaluate the impact of polyethylene glycol (PEG) and zwitterionic surface decoration lipid-based nanocarriers (NC) on cellular uptake.Anionic, neutral cationic NCs based lecithin were compared with conventional PEGylated regarding stability in biorelevant fluids, interaction endosome mimicking membranes, cytocompatibility, uptake permeation across intestinal mucosa.PEGylated exhibited a droplet size between 100 125 nm narrow distribution. For only minor alterations PDI fasted state fluid mucus containing buffer observed, demonstrating similar bioinert properties. Erythrocytes studies revealed enhanced endosomal escape properties for to NCs. negligible cytotoxicity Caco-2 HEK cells, even highest tested concentration 1 % (v/v) was recorded. The showed cell survival ≥75 concentrations ≤0.05 which considered as non-toxic. up 60-fold higher cells determined 58.5 40.0 respectively, determined. results confirmed visually by life imaging. Ex-vivo experiments using rat mucosa demonstrated 8.6-fold lipophilic marker coumarin-6 control. Up 6.9-fold counterpart recorded.The replacement PEG surfactants is promising approach overcome drawbacks intracellular drug delivery.

Язык: Английский

Процитировано

15
Advanced approaches in skin wound healing – a review on the multifunctional properties of MXenes in therapy and sensing DOI Creative Commons

Valeria Ferrara,

Caterina Perfili,

Giulia Artemi

и другие.

Nanoscale, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

In recent years, the use of MXenes, a class two-dimensional materials composed transition metal carbides, nitrides, or carbonitrides, has shown significant promise in field skin wound healing. This review explores multifunctional properties focusing on their electrical conductivity, photothermal effects, and biocompatibility this field. MXenes have been utilized to develop advanced healing devices such as hydrogels, patches, smart bandages for examination. These offer enhanced antibacterial activity, promote tissue regeneration, provide real-time monitoring parameters. The highlights synthesis methods, chemical features, biological effects emphasizing role innovative repair strategies. Additionally, it discusses potential MXene-based sensors humidity, pH, temperature monitoring, which are crucial preventing infections complications integration into wearable represents advancement management, promising improved clinical outcomes quality life patients.

Язык: Английский

Процитировано

6