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1.
Encyclopedia ; 1(3):773, 2021.
Article in English | ProQuest Central | ID: covidwho-1834750

ABSTRACT

DefinitionCOVID-19 mRNA vaccines contain synthetic mRNA sequences encoded for the Spike proteins expressed on the surface of SARS-CoV-2, and utilize the host cells to produce specific antigens that stimulate both humoral and cellular immunities. Lipid nanoparticles are essential to facilitate the intracellular delivery of the mRNA to its action site, the ribosome, to fully exert its effect.

2.
AAPS PharmSciTech ; 23(5): 135, 2022 May 09.
Article in English | MEDLINE | ID: covidwho-1833435

ABSTRACT

Lipid nanoparticles (LNPs) can be used as delivery vehicles for nucleic acid biotherapeutics. In fact, LNPs are currently being used in the Pfizer/BioNTech and Moderna COVID-19 vaccines. Cationic LNPs composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (chol) LNPs have been classified as one of the most efficient gene delivery systems and are being tested in numerous clinical trials. The objective of this study was to examine the effect of the molar ratio of DOTAP/chol, PEGylation, and lipid to mRNA ratio on mRNA transfection, and explore the applications of DOTAP/chol LNPs in pDNA and oligonucleotide transfection. Here we showed that PEGylation significantly decreased mRNA transfection efficiency of DOTAP/chol LNPs. Among non-PEGylated LNP formulations, 1:3 molar ratio of DOTAP/chol in DOTAP/chol LNPs showed the highest mRNA transfection efficiency. Furthermore, the optimal ratio of DOTAP/chol LNPs to mRNA was tested to be 62.5 µM lipid to 1 µg mRNA. More importantly, these mRNA-loaded nanoparticles were stable for 60 days at 4 °C storage without showing reduction in transfection efficacy. We further found that DOTAP/chol LNPs were able to transfect pDNA and oligonucleotides, demonstrating the ability of these LNPs to transport the cargo into the cell nucleus. The influence of various factors in the formulation of DOTAP/chol cationic LNPs is thus described and will help improve drug delivery of nucleic acid-based vaccines and therapies.


Subject(s)
COVID-19 , Nanoparticles , COVID-19 Vaccines , Cations , Cholesterol , Fatty Acids, Monounsaturated , Humans , Liposomes , Oligonucleotides , Propane , Quaternary Ammonium Compounds , RNA, Messenger/genetics
3.
Biomaterials ; 286: 121570, 2022 May 07.
Article in English | MEDLINE | ID: covidwho-1821147

ABSTRACT

The mRNA vaccine technology has promising applications to fight infectious diseases as demonstrated by the licensing of two mRNA-based vaccines, Comirnaty® (Pfizer/BioNtech) and Spikevax® (Moderna), in the context of the Covid-19 crisis. Safe and effective delivery systems are essential to the performance of these vaccines and lipid nanoparticles (LNPs) able to entrap, protect and deliver the mRNA in vivo are considered by many as the current "best in class". Nevertheless, current mRNA/LNP vaccine technology has still some limitations, one of them being thermostability, as evidenced by the ultracold distribution chain required for the licensed vaccines. We found that the thermostability of mRNA/LNP, could be improved by a novel imidazole modified lipid, DOG-IM4, in combination with standard helper lipids. DOG-IM4 comprises an ionizable head group consisting of imidazole, a dioleoyl lipid tail and a short flexible polyoxyethylene spacer between the head and tail. Here we describe the synthesis of DOG-IM4 and show that DOG-IM4 LNPs confer strong immunization properties to influenza HA mRNA in mice and macaques and a remarkable stability to the encapsulated mRNA when stored liquid in phosphate buffered saline at 4 °C. We speculate the increased stability to result from some specific attributes of the lipid's imidazole head group.

4.
Advanced Nanobiomed Research ; 2(2):17, 2022.
Article in English | Web of Science | ID: covidwho-1813459

ABSTRACT

Lipid nanoparticles have attracted significant interests in the last two decades, and have achieved tremendous clinical success since the first clinical approval of Doxil in 1995. At the same time, lipid nanoparticles have also demonstrated enormous potential in delivering nucleic acid drugs as evidenced by the approval of two RNA therapies and mRNA COVID-19 vaccines. In this review, an overview on different classes of lipid nanoparticles, including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, is first provided, followed by the introduction of their preparation methods. Then the characterizations of lipid nanoparticles are briefly reviewed and their applications in encapsulating and delivering hydrophobic drugs, hydrophilic drugs, and RNAs are highlighted. Finally, various applications of lipid nanoparticles for overcoming different delivery challenges, including crossing the blood-brain barrier, targeted delivery, and various routes of administration, are summarized. Lipid nanoparticles as drug delivery systems offer many attractive benefits such as great biocompatibility, ease of preparation, feasibility of scale-up, nontoxicity, and targeted delivery, while current challenges in drug delivery warrant future studies about structure-function correlations, large-scale production, and targeted delivery to realize the full potential of lipid nanoparticles for wider clinical and pharmaceutical applications in future.

5.
ACS Nano ; 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1805555

ABSTRACT

There is a growing interest in the development of lipid-based nanocarriers for multiple purposes, including the recent increase of these nanocarriers as vaccine components during the COVID-19 pandemic. The number of studies that involve the surface modification of nanocarriers to improve their performance (increase the delivery of a therapeutic to its target site with less off-site accumulation) is enormous. The present review aims to provide an overview of various methods associated with lipid nanoparticle grafting, including techniques used to separate grafted nanoparticles from unbound ligands or to characterize grafted nanoparticles. We also provide a critical perspective on the usefulness and true impact of these modifications on overcoming different biological barriers, with our prediction on what to expect in the near future in this field.

6.
Adv Drug Deliv Rev ; 184: 114197, 2022 05.
Article in English | MEDLINE | ID: covidwho-1763526

ABSTRACT

Gene therapy has emerged as a potential platform for treating several dreaded and rare diseases that would not have been possible with traditional therapies. Viral vectors have been widely explored as a key platform for gene therapy due to their ability to efficiently transport nucleic acid-based therapeutics into the cells. However, the lack of precision in their delivery has led to several off-target toxicities. As such, various strategies in the form of non-viral gene delivery vehicles have been explored and are currenlty employed in several therapies including the SARS-CoV-2 vaccine. In this review, we discuss the opportunities lipid nanoparticles (LNPs) present for efficient gene delivery. We also discuss various synthesis strategies via microfluidics for high throughput fabrication of non-viral gene delivery vehicles. We conclude with the recent applications and clinical trials of these vehicles for the delivery of different genetic materials such as CRISPR editors and RNA for different medical conditions ranging from cancer to rare diseases.


Subject(s)
COVID-19 , Nanoparticles , Nucleic Acids , COVID-19 Vaccines , Humans , Lipids , Liposomes , Microfluidics , Rare Diseases , SARS-CoV-2
7.
J Control Release ; 345: 314-333, 2022 May.
Article in English | MEDLINE | ID: covidwho-1751089

ABSTRACT

Since its outbreak in late 2019, the novel coronavirus disease 2019 (COVID-19) has spread to every continent on the planet. The global pandemic has affected human health and socioeconomic status around the world. At first, the global response to the pandemic was to isolate afflicted individuals to prevent the virus from spreading, while vaccine development was ongoing. The genome sequence was first presented in early January 2020, and the phase I clinical trial of the vaccine started in March 2020 in the United States using novel lipid-based nanoparticle (LNP), encapsulated with mRNA termed as mRNA-1273. Till now, various mRNA-based vaccines are in development, while one mRNA-based vaccine got market approval from US-FDA for the prevention of COVID-19. Previously, mRNA-based vaccines were thought to be difficult to develop, but the current development is a significant accomplishment. However, widespread production and global availability of mRNA-based vaccinations to combat the COVID-19 pandemic remains a major challenge, especially when the mutations continually occur on the virus (e.g., the recent outbreaks of Omicron variant). This review elaborately discusses the COVID-19 pandemic, the biology of SARS-CoV-2 and the progress of mRNA-based vaccines. Moreover, the review also highlighted a detailed description of mRNA delivery technologies and the application potential in controlling other life-threatening diseases. Therefore, it provides a comprehensive view and multidisciplinary insights into mRNA therapy for broader audiences.

8.
Cell Rep ; 38(11): 110514, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1739598

ABSTRACT

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.


Subject(s)
AIDS Vaccines , COVID-19 , HIV-1 , Nanoparticles , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing , COVID-19 Vaccines , Epitopes , Ferritins/genetics , HIV Antibodies , Humans , Liposomes , Mice , RNA, Messenger , env Gene Products, Human Immunodeficiency Virus/genetics
9.
Drug Deliv Transl Res ; 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1739444

ABSTRACT

The triumphant success of mRNA vaccines is a testimony to the important role drug delivery technologies have played in protecting billions of people against SARS-CoV-2 (or the Corona Virus Disease 2019; COVID-19). Several lipid nanoparticle (LNP) mRNA vaccines were developed and have been instrumental in preventing the disease by boosting the immune system against the pathogen, SARS-CoV-2. These vaccines have been built on decades of scientific research in drug delivery of mRNA, vaccines, and other biologicals. In this manuscript, several leading and emerging scientists in the field of drug delivery share their perspective on the role of drug delivery technologies in developing safe and efficacious vaccines, in a roundtable discussion. The authors also discussed their viewpoint on the current challenges, and the key research questions that should drive this important area of research.

10.
Mol Pharm ; 19(4): 1047-1058, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1721386

ABSTRACT

The coronavirus disease of 2019 (COVID-19) pandemic launched an unprecedented global effort to rapidly develop vaccines to stem the spread of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). Messenger ribonucleic acid (mRNA) vaccines were developed quickly by companies that were actively developing mRNA therapeutics and vaccines for other indications, leading to two mRNA vaccines being not only the first SARS-CoV-2 vaccines to be approved for emergency use but also the first mRNA drugs to gain emergency use authorization and to eventually gain full approval. This was possible partly because mRNA sequences can be altered to encode nearly any protein without significantly altering its chemical properties, allowing the drug substance to be a modular component of the drug product. Lipid nanoparticle (LNP) technology required to protect the ribonucleic acid (RNA) and mediate delivery into the cytoplasm of cells is likewise modular, as are technologies and infrastructure required to encapsulate the RNA into the LNP. This enabled the rapid adaptation of the technology to a new target. Upon the coattails of the clinical success of mRNA vaccines, this modularity will pave the way for future RNA medicines for cancer, gene therapy, and RNA engineered cell therapies. In this review, trends in the publication records and clinical trial registrations are tallied to show the sharp intensification in preclinical and clinical research for RNA medicines. Demand for the manufacturing of both the RNA drug substance (DS) and the LNP drug product (DP) has already been strained, causing shortages of the vaccine, and the rise in development and translation of other mRNA drugs in the coming years will exacerbate this strain. To estimate demand for DP manufacturing, the dosing requirements for the preclinical and clinical studies of the two approved mRNA vaccines were examined. To understand the current state of mRNA-LNP production, current methods and technologies are reviewed, as are current and announced global capacities for commercial manufacturing. Finally, a vision is rationalized for how emerging technologies such as self-amplifying mRNA, microfluidic production, and trends toward integrated and distributed manufacturing will shape the future of RNA manufacturing and unlock the potential for an RNA medicine revolution.


Subject(s)
COVID-19 , COVID-19 Vaccines , Humans , Liposomes , Nanoparticles , RNA, Messenger/metabolism , SARS-CoV-2/genetics
11.
J Med Virol ; 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1718374

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer-BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long-term effects and to assess the vaccine safety and efficacy in the general population.

12.
Pharmakeftiki ; 33(3):190-199, 2021.
Article in English | Scopus | ID: covidwho-1695205

ABSTRACT

Vaccination has had a tremendous impact on global health and the quality of human life by reducing the mortality and morbidity caused by infectious diseases. However, effective and therapeutic vaccines have yet to be developed for completely carrying deadly diseases. In the past few decades, there has been increasing focus on the field of nanotechnology in the combination with vaccination. Nanovaccine formulations not only provide enhanced antigen stability and immunogenicity but also offer targeted delivery and prolonged release. A high number of NP vaccines with varied physicochemical characteristics and properties have been approved for clinical use. The initial part of this review provides information about lipid-based nanoparticles in which nucleic acids such as DNA (as plasmids) and RNA (as mRNA) are encapsulated in order to be used for vaccination. Subsequently, there is presented a short overview according to the first lipid-based marketed products, Inflexal V and Epaxal, and their correlation with today’s lipid-based nanovaccines. This review also focuses on the research efforts for the development of lipid-based vaccines against SARS, MERS and of the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19. Finally, there are highlighted the promising new treatments and future perspectives of these nanovaccines. © 2021, Zita Medical Managent. All rights reserved.

13.
Int J Mol Sci ; 23(5)2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1699203

ABSTRACT

Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.


Subject(s)
COVID-19/therapy , Drug Delivery Systems/methods , Nanoparticles/administration & dosage , RNA, Small Interfering/administration & dosage , RNAi Therapeutics/methods , Animals , COVID-19/epidemiology , COVID-19/virology , Humans , Models, Genetic , Nanoparticles/chemistry , Pandemics/prevention & control , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics , SARS-CoV-2/physiology
14.
J Control Release ; 344: 80-96, 2022 04.
Article in English | MEDLINE | ID: covidwho-1693301

ABSTRACT

In 2021, mRNA vaccines against COVID-19 were approved by the Food and Drug Administration. mRNA vaccines are important for preventing severe COVID-19 and returning to normal life. The development of RNA-delivery technology, including mRNA vaccines, has been investigated worldwide for ~30 years. Lipid nanoparticles (LNPs) are a breakthrough technology that stably delivers RNA to target organs, and RNA-loaded LNP-based nanomedicines have been studied for the development of vaccines and nanomedicines for RNA-, gene-, and cell-based therapies. Recently, microfluidic devices and technologies have attracted attention for the production of LNPs, particularly RNA-loaded LNPs. Microfluidics provides many advantages for RNA-loaded LNP production, including precise LNP size controllability, high reproducibility, high-throughput optimization of LNP formulation, and continuous LNP-production processes. In this review, we summarize microfluidic-based RNA-loaded LNP production and its applications in RNA-based therapy and genome editing.


Subject(s)
COVID-19 , Nanoparticles , COVID-19 Vaccines , Humans , Lipids , Liposomes , Microfluidics , RNA, Small Interfering/genetics , Reproducibility of Results
15.
Pharmaceutics ; 14(2)2022 Feb 11.
Article in English | MEDLINE | ID: covidwho-1686917

ABSTRACT

The world raced to develop vaccines to protect against the rapid spread of SARS-CoV-2 infection upon the recognition of COVID-19 as a global pandemic. A broad spectrum of candidates was evaluated, with mRNA-based vaccines emerging as leaders due to how quickly they were available for emergency use while providing a high level of efficacy. As a modular technology, the mRNA-based vaccines benefitted from decades of advancements in both mRNA and delivery technology prior to the current global pandemic. The fundamental lessons of the utility of mRNA as a therapeutic were pioneered by Dr. Katalin Kariko and her colleagues, perhaps most notably in collaboration with Drew Weissman at University of Pennsylvania, and this foundational work paved the way for the development of the first ever mRNA-based therapeutic authorized for human use, COMIRNATY®. In this Special Issue of Pharmaceutics, we will be honoring Dr. Kariko for her great contributions to the mRNA technology to treat diseases with unmet needs. In this review article, we will focus on the delivery platform, the lipid nanoparticle (LNP) carrier, which allowed the potential of mRNA therapeutics to be realized. Similar to the mRNA technology, the development of LNP systems has been ongoing for decades before culminating in the success of the first clinically approved siRNA-LNP product, ONPATTRO®, a treatment for an otherwise fatal genetic disease called transthyretin amyloidosis. Lessons learned from the siRNA-LNP experience enabled the translation into the mRNA platform with the eventual authorization and approval of the mRNA-LNP vaccines against COVID-19. This marks the beginning of mRNA-LNP as a pharmaceutical option to treat genetic diseases.

16.
Chem Phys Lipids ; 243: 105178, 2022 03.
Article in English | MEDLINE | ID: covidwho-1664753

ABSTRACT

Lipid nanoparticles (LNPs) mediated mRNA delivery has gained prominence due to the success of mRNA vaccines against Covid-19, without which it would not have been possible. However, there is little clinical validation of this technology for other mRNA-based therapeutic approaches. Systemic administration of LNPs predominantly targets the liver, but delivery to other organs remains a challenge. Local approaches remain a viable option for some disease indications, such as Cystic Fibrosis, where aerosolized delivery to airway epithelium is the preferred route of administration. With this in mind, novel cationic lipids (L1-L4) have been designed, synthesized and co-formulated with a proprietary ionizable lipid. These LNPs were further nebulized, along with baseline control DOTAP-based LNP (DOTAP+), and tested in vitro for mRNA integrity and encapsulation efficiency, as well as transfection efficiency and cytotoxicity in cell cultures. Improved biodegradability and potentially superior elimination profiles of L1-L4, in part due to physicochemical characteristics of putative metabolites, are thought to be advantageous for prospective therapeutic lung delivery applications using these lipids.


Subject(s)
Liposomes/chemistry , Lung , Nanoparticles/chemistry , RNA, Messenger/administration & dosage , Humans
17.
Pharmaceutics ; 14(1)2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1630127

ABSTRACT

The emerging pathogen Candida auris is an emerging fungal pathogen that was associated with nosocomial infectious outbreaks. Its worldwide incidence and the emerging multidrug-resistant strains highlight the urgency for novel and effective antifungal treatment strategies. Lippia sidoides essential oil (LSEO) proved antifungal activity, including anti-Candida. However, it may undergo irreversible changes when in contact with external agents without adequate protection. Herein, we encapsulated LSEO in nanostructured lipid carriers (NLC) through the hot emulsification method followed by sonication. NLC matrix was based on oleic acid and Compritol® 888, or a combination of carnauba wax and beeswax, stabilized by sodium dodecyl sulfate. Eight formulations were produced and characterized by the determination of the particle size (213.1 to 445.5 nm), polydispersity index (around 0.3), and ζ-potential (-93.1 to -63.8 mV). The antifungal activity of nanoparticles and LSEO against C. auris and the in vivo toxicity in Galleria mellonella model were also evaluated. Both NLC and LSEO exhibited potent activity against the yeast, with Minimum Inhibitory Concentration between 281 and 563 µg/mL, and did not evidence toxicity in the in vivo model. Therefore, this study confirms the viability of NLCs loaded with LSEO in combating drug-resistant pathogens as a potential new therapeutic strategy for managing of candidemia.

18.
Nano Today ; 43: 101403, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1636284

ABSTRACT

BioNTech/Pfizer's Comirnaty and Moderna's SpikeVax vaccines consist in mRNA encapsulated in lipid nanoparticles (LNPs). The modularity of the delivery platform and the manufacturing possibilities provided by microfluidics let them look like an instant success, but they are the product of decades of intense research. There is a multitude of considerations to be made when designing an optimal mRNA-LNPs vaccine. Herein, we provide a brief overview of what is presently known and what still requires investigation to optimize mRNA LNPs vaccines. Lastly, we give our perspective on the engineering of 3D bioprinted validation systems that will allow faster, cheaper, and more predictive vaccine testing in the future compared with animal models.

19.
Materials (Basel) ; 15(2)2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1625555

ABSTRACT

Currently, carriers of active ingredients in the form of particles of a size measured in nanometers are the focus of interest of research centers worldwide. So far, submicrometer emulsions, liposomes, as well as microspheres, and nanospheres made of biodegradable polymers have been used in medicine. Recent studies show particular interest in nanoparticles based on lipids, and at the present time, are even referred to as the "era of lipid carriers". With the passage of time, lipid nanoparticles of the so-called first and second generation, SLN (Solid Lipid Nanoparticles) and nanostructured lipid carriers and NLC (Nanostructured Lipid Carriers), respectively, turned out to be an alternative for all imperfections of earlier carriers. These carriers are characterized by a number of beneficial functional properties, including, among others, structure based on lipids well tolerated by the human body, high stability, and ability to carry hydro- and lipophilic compounds. Additionally, these carriers can enhance the distribution of the drug in the target organ and alter the pharmacokinetic properties of the drug carriers to enhance the medical effect and minimize adverse side effects. This work is focused on the current review of the state-of-the-art related to the synthesis and applications of popular nanoparticles in medicine, with a focus on their use, e.g., in COVID-19 vaccines.

20.
Curr Med Chem ; 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1607668

ABSTRACT

This review describes the use of Lipid-based Nanocarriers (LNCs) for the parenteral delivery of pharmaceutical actives. Firstly, the two generation of LNCs such as ''solid lipid nanoparticles'' (SLNs) and ''nanostructured lipid carriers'' (NLCs) are explained in term of preparation, characterization and stability. Although the use of LNCs through parenteral administration has shown many benefits, their use is limited by opsonization, an immune process that causes their short half-life (3-5 min). Therefore, many strategies are discussed to realize "stealth" systems suitable for parenteral administration. Successfully, the requirements and applications of parenteral lipid nanoparticles are reviewed for the delivery of natural compounds, synthetic drugs and genetic materials. In the last period, the latter application has been a remarkable interest due to the numerous benefits of mRNA vaccines to fight the Covid-19 pandemic.

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