A perspective of lipid nanoparticles for RNA delivery

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: April 15, 2024

Abstract Over the last two decades, lipid nanoparticles (LNPs) have evolved as an effective biocompatible and biodegradable RNA delivery platform in fields of nanomedicine, biotechnology, drug delivery. They are novel bionanomaterials that can be used to encapsulate a wide range biomolecules, such mRNA, demonstrated by current successes COVID‐19 mRNA vaccines. Therefore, it is important provide perspective on LNPs for delivery, which further offers useful guidance researchers who want work RNA‐based LNP field. This first summarizes approaches preparation LNPs, followed introduction key characterization parameters. Then, vitro cell experiments study performance, including selection, viability, cellular association/uptake, endosomal escape, their efficacy, were summarized. Finally, vivo animal aspects administration, dosing safety, therapeutic efficacy discussed. The authors hope this offer valuable enter field help them understand crucial parameters demand.

Language: Английский

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Biomaterials Based on Organic Polymers and Layered Double Hydroxides Nanocomposites: Drug Delivery and Tissue Engineering

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 413 - 413

Published: Jan. 26, 2023

The development of biomaterials has a substantial role in pharmaceutical and medical strategies for the enhancement life quality. This review work focused on versatile based nanocomposites comprising organic polymers class layered inorganic nanoparticles, aiming drug delivery (oral, transdermal, ocular delivery) tissue engineering (skin bone therapies). Layered double hydroxides (LDHs) are 2D nanomaterials that can intercalate anionic bioactive species between layers. layers hold metal cations confer intrinsic biological activity to LDHs as well biocompatibility. intercalation allows formation systems with elevated loading capacity modified release profiles promoted by ion exchange and/or solubilization. integration, antigenicity, stimulation collagen formation, among other beneficial characteristics LDH, have been observed vivo assays. association properties biocompatible LDH-drug nanohybrids produces multifunctional compatible living matter. Such stimuli-responsive, show appropriate mechanical properties, be prepared creative methods allow fine-tuning release. They processed end form films, beads, gels, monoliths etc., reach orientated therapeutic applications. Several studies attest higher performance polymer/LDH-drug nanocomposite compared hybrid or free drug.

Language: Английский

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Bioinspired Spatiotemporal Management toward RNA Therapies

ACS Nano, Journal Year: 2023, Volume and Issue: 17(24), P. 24539 - 24563

Published: Dec. 13, 2023

Ribonucleic acid (RNA)-based therapies have become an attractive topic in disease intervention, especially with some that been approved by the FDA such as mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech, and Spikevax, Moderna) Patisiran (siRNA-based drug for liver delivery). However, extensive applications are still facing challenges delivering highly negatively charged RNA to targeted site. Therapeutic delivery strategies including modifications, conjugates, polyplexes platforms viral vectors, nanoparticle-based platforms, hydrogel-based potential nucleic acid-releasing depots developed enhance their cellular uptake protect from being degraded immune systems. Here, we review growing number of nanoparticles, systems; describe loading/release mechanism induced environmental stimulations light, heat, pH, or enzyme; discuss physical chemical interactions; summarize therapeutics release period (temporal) target cells/organs (spatial). Finally, current concerns, highlight future perspectives RNA-based systems, provide possible research areas opportunities clinical translation carriers.

Language: Английский

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Validation of an HPLC-CAD Method for Determination of Lipid Content in LNP-Encapsulated COVID-19 mRNA Vaccines

Vaccines, Journal Year: 2023, Volume and Issue: 11(5), P. 937 - 937

Published: May 4, 2023

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs determined by the properties contents various lipids in formulation system, efficiency largely depends on lipid composition. For quality control such vaccines, here we developed validated an HPLC-CAD method to identify determine four LNP-encapsulated COVID-19 vaccine support analysis development new drugs

Language: Английский

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mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Dec. 18, 2024

Abstract Harnessing the power of immune system to target cancer cells is one most appealing approaches for therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) vaccines are worthy consideration, as they have demonstrated promising results in clinical trials. These proven be safe and well-tolerated. They can easily mass-produced a relatively short time induce systemic response effective against both primary tumor metastases. Transcripts encoding immunomodulatory molecules also incorporated into mRNA, enhancing its efficacy. On other hand, there some challenges associated with their application, including mRNA instability, insufficient uptake by cells, intrinsic immunogenicity, which block translation. Many innovations been suggested overcome obstacles, structural modification (such 5’ cap modification), optimizing delivery vehicles (especially dendritic (DCs) nanoparticles), using antigens that enhance immunogenicity circumventing tolerance mechanisms. A popular approach combine traditional novel treatments like chemotherapy, radiotherapy, checkpoint blockade (ICB). efficacious when combined therapies ICBs. There still long way go before enter standard care patients, but incredible pace development this field, application will soon witnessed. This review highlights recent advances vaccines. Finally, prominent applications reviewed.

Language: Английский

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Safety and Tolerability of COVID-19 Vaccine in Mast Cell Disorders Real-Life Data from a Single Centre in Italy

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 202 - 202

Published: Feb. 16, 2024

Background In the past three years, COVID-19 has had a significant impact on healthcare systems and people’s safety worldwide. Mass vaccinations dramatically improved health economic damage caused by SARS-CoV-2. However, of vaccines in patients at high risk allergic reactions still many unmet needs that should be clarified. Material methods A retrospective, single-centre study was performed collecting demographic clinical data with Mast Cell Disorders (MCDs) to evaluate tolerability vaccinations. Moreover, any changes natural history underlying disease following vaccine have been evaluated. Results This included 66 affected MCDs. Out them, 52 (78.8%) received vaccination 41 completed course. Premedication came first 86.6% our patients. total seven (4.5%) complained about an immediate reaction two (1.3%) late reaction. Worsening MCD observed single patient. Conclusions Despite overall reactions, did not reveal increased for SARS-CoV-2 patients, thus supporting recommendation favour vaccination. due potentially rate anaphylactic receive premedication treated hospital setting after allergological specialistic evaluation.

Language: Английский

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ATAK Complex (Adrenaline, Takotsubo, Anaphylaxis, and Kounis Hypersensitivity-Associated Coronary Syndrome) after COVID-19 Vaccination and Review of the Literature

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 322 - 322

Published: Jan. 31, 2023

Anaphylactic events triggered by mRNA COVID-19 vaccines are neither serious nor frequent. Kounis syndrome is described as the concomitant occurrence of acute coronary and hypersensitivity reactions induced vasospastic mediators after an allergic event. caused very rare. Up to now, only a few cases myocardial infarction vaccine administration have been reported. Takotsubo cardiomyopathy characterized transient wall movement abnormalities left ventricular apex, mid-ventricle, or other distribution, usually intense emotional physical stress. has reported, with delayed onset. A new entity association adrenaline administration, cardiomyopathy, anaphylaxis, was recently described: ATAK complex. Here, we report case that occurred together anaphylactic reaction required use adrenaline. The timing referenced clinical symptoms could not exclude idea occurred. Therefore, can assume patient presented We believe highlighting on this complex will aid application proper diagnostic, preventive therapeutic measures.

Language: Английский

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The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis

Allergy and Asthma Proceedings, Journal Year: 2024, Volume and Issue: 45(6), P. 438 - 446

Published: Nov. 1, 2024

Background: Adverse allergic reactions due to the administration of vaccines developed for protection coronavirus disease 2019 (COVID-19) have been reported since initiation vaccination campaigns in December 15, 2020. Current analyses provided by Centers Disease Control and Prevention U.S. Food Drug Administration United States estimated rates anaphylactic 2.5 11.1 per million messenger RNA (mRNA) 1273 BNT162b2 administered, respectively. The mechanisms which these mRNA induce adverse vaccine subject conflicting reports. Although skin testing with excipient components found mRNA-1273 vaccines, such as polyethylene glycol (PEG) related lipid products, were originally recommended identify potential predictive biomarkers reactions, more recent evidence has suggested that routine excipients poor predictability do not correlate susceptibility injury. Objective: goal this proof-of-concept (POC) exploratory study was investigate role leukocyte activation (LA) induced COVID-19 pathogenesis vaccine‐associated using an LA assay our laboratory. Results: An performed on blood samples obtained from 30 subjects who assigned three groups: group 1 consisted 10 had received a serious reaction; 2 mild 3 asymptomatic. Five tested each subjects; hence, 50 could be expressed groups. In shown clinically severe effects, 8 (16%) index (LAI) responses (>144.83), 12 (24%) moderate LAI (87.62 ‐144.82), (60%) no reaction (0 ‐ 87.61). 4 (8%) 9 (18%) 37 (74%) reaction. and, therefore, clinical (4%) (20%) 38 (76%) responses. Conclusion: results POC suggest measurement PEG other vaccine-related may provide novel useful biomarker associated non‐immunoglobulin E (IgE) vaccines. also underscore growing concerns non-IgE hypersensitivity their reactions. This is particularly noteworthy because, continuing emergence evolving variants acute respiratory syndrome corona-virus mutants, yearly immunization will most likely recommended. sufficiently powered draw definitive conclusions regard associations between vaccine-associated LA, trends set seen reactivity scores, ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), benefit worthy exploration future randomized controlled trials.

Language: Английский

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Association of the Magnitude of Anti-SARS-CoV-2 Vaccine Side Effects with Sex, Allergy History, Chronic Diseases, Medication Intake, and SARS-CoV-2 Infection

Vaccines, Journal Year: 2024, Volume and Issue: 12(1), P. 104 - 104

Published: Jan. 20, 2024

Vaccination provides the best protection against increasing infections of SARS-CoV-2. The magnitude and type anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, associations between different SEs age, sex, presence chronic diseases, medication intake, history allergies, with SARS-CoV-2 were investigated. Our survey used Google platform had 866 participants, contacted through e-mails, social media chain referral sampling (margin error ≈ 4.38%, 99% confidence). More than participants received BNT162b2 ChAdOx1-S vaccines. Being female, having taking medicines routinely a infection (p < 0.05) associated strong after second dose. Having allergies female sex 0.01) Furthermore, results reveal, for first time, usage, Additionally, study supports association an increased potential developing stronger certain

Language: Английский

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General Workflow for Studying Performance of RNA-Based Lipid Nanoparticles

Authorea (Authorea), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

Over the last two decades, lipid nanoparticles (LNPs) have evolved as an effective biocompatible and biodegradable RNA delivery platform in field of nanomedicine, biotechnology drug delivery, with current successes COVID-19 mRNA vaccines. Therefore, it is important to provide a general workflow studying RNA-based LNP performance, which further offers useful guidance for researchers who want work field. In this perspective, we first summarized approaches preparation LNPs, followed by introduction key characterization parameters. Then, vitro evaluation performance including cell selection, viability, cellular association/uptake, endosomal escape their efficacy was summarized. Finally, vivo assessment aspects animal administration, dosing safety, therapeutic discussed. We hope perspective can offer valuable enter LNPs help them understand crucial parameters that demands.

Language: Английский

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