Ermilova, Inna et al. published their research in Physical Chemistry Chemical Physics in 2020 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Esters contain a carbonyl center, which gives rise to 120掳 C鈥揅鈥揙 and O鈥揅鈥揙 angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C鈥揙鈥揅 bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Reference of 1224606-06-7

DOPC versus DOPE as a helper lipid for gene-therapies: molecular dynamics simulations with DLin-MC3-DMA was written by Ermilova, Inna;Swenson, Jan. And the article was included in Physical Chemistry Chemical Physics in 2020.Reference of 1224606-06-7 The following contents are mentioned in the article:

Ionizable lipids are important compounds of modern therapeutic lipid nano-particles (LNPs). One of the most promising ionizable lipids (or amine lipids) is DLin-MC3-DMA. Depending on their pharmaceutical application these LNPs can also contain various helper lipids, such as phospho- and pegylated lipids, cholesterol and nucleic acids as a cargo. Due to their complex compositions the structures of these therapeutics have not been refined properly. Therefore, the role of each lipid in the pharmacol. properties of LNPs has not been determined In this work an atomistic model for the neutral form of DLin-MC3-DMA was derived and all-atom mol. dynamics (MD) simulations were carried out in order to investigate the effect of the phospholipid headgroup on the possible properties of the shell-membranes of LNPs. Bilayers containing either DOPC or DOPE lipids at two different ratios of DLin-MC3-DMA (5 mol% and 15 mol%) were constructed and simulated at neutral pH 7.4. The results from the anal. of MD trajectories revealed that DOPE lipid headgroups associated strongly with lipid tails and carbonyl oxygens of DLin-MC3-DMA, while for DOPC lipid headgroups no significant associations were observed Furthermore, the strong associations between DOPE and DLin-MC3-DMA result in the positioning of DLin-MC3-DMA at the surface of the membrane. Such an interplay between the lipids slows down the lateral diffusion of all simulated bilayers, where a more dramatic decrease of the diffusion rate is observed in membranes with DOPE. This can explain the low water penetration of lipid bilayers with phosphatidylethanolamines and, probably, can relate to the bad transfection properties of LNPs with DOPE and DLin-MC3-DMA. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Reference of 1224606-06-7).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Esters contain a carbonyl center, which gives rise to 120掳 C鈥揅鈥揙 and O鈥揅鈥揙 angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C鈥揙鈥揅 bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Reference of 1224606-06-7

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Arteta, Marianna Yanez et al. published their research in Proceedings of the National Academy of Sciences of the United States of America in 2018 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is 纬-valerolactone.Synthetic Route of C43H79NO2

Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles was written by Arteta, Marianna Yanez;Kjellman, Tomas;Bartesaghi, Stefano;Wallin, Simonetta;Wu, Xiaoqiu;Kvist, Alexander J.;Dabkowska, Aleksandra;Szekely, Noemi;Radulescu, Aurel;Bergenholtz, Johan;Lindfors, Lennart. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2018.Synthetic Route of C43H79NO2 The following contents are mentioned in the article:

The development of safe and efficacious gene vectors has limited greatly the potential for therapeutic treatments based on mRNA (mRNA). Lipid nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA), helper lipids (distearoylphosphatidylcholine, DSPC, and cholesterol), and a poly(ethylene glycol) (PEG) lipid have been identified as very promising delivery vectors of short interfering RNA (siRNA) in different clin. phases; however, delivery of high-mol. weight RNA has been proven much more demanding. Herein we elucidate the structure of hEPO modified mRNA-containing LNPs of different sizes and show how structural differences affect transfection of human adipocytes and hepatocytes, two clin. relevant cell types. Employing smallangle scattering, we demonstrate that LNPs have a disordered inverse hexagonal internal structure with a characteristic distance around 6 nm in presence of mRNA, whereas LNPs containing no mRNA do not display this structure. Furthermore, using contrast variation small-angle neutron scattering, we show that one of the lipid components, DSPC, is localized mainly at the surface of mRNAcontaining LNPs. By varying LNP size and surface composition we demonstrate that both size and structure have significant influence on intracellular protein production As an example, in both human adipocytes and hepatocytes, protein expression levels for 130 nm LNPs can differ as much as 50-fold depending on their surface characteristics, likely due to a difference in the ability of LNP fusion with the early endosome membrane.We consider these discoveries to be fundamental and opening up new possibilities for rational design of synthetic nanoscopic vehicles for mRNA delivery. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Synthetic Route of C43H79NO2).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is 纬-valerolactone.Synthetic Route of C43H79NO2

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Gindy, Marian E. et al. published their research in Molecular Pharmaceutics in 2014 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Acyl chlorides and acid anhydrides alcoholysis is another way to produce esters. Acyl chlorides and acid anhydrides react with alcohols to produce esters. Anydrous conditions are recommended since both acyl chlorides and acid anhydrides react with water.Application of 1224606-06-7

Stabilization of Ostwald Ripening in Low Molecular Weight Amino Lipid Nanoparticles for Systemic Delivery of siRNA Therapeutics was written by Gindy, Marian E.;Feuston, Brad;Glass, Angela;Arrington, Leticia;Haas, R. Matthew;Schariter, Joseph;Stirdivant, Steven M.. And the article was included in Molecular Pharmaceutics in 2014.Application of 1224606-06-7 The following contents are mentioned in the article:

Lipid nanoparticles (LNPs) represent the most clin. advanced technol. for the systemic delivery of therapeutic siRNA in vivo. Toward this end, a novel class of LNPs comprising low mol. weight (MW) ionizable amino lipids having asym. architecture was recently reported. LNPs of these amino lipids, termed asym. LNPs, were shown to be highly efficacious and well tolerated in vivo; advances were enabled by improved endosomal escape, coupled with enhanced amino lipid metabolism and clearance. In this work, we show that, in contrast to their desirable pharmacol. performance, asym. LNPs present a significant pharmaceutical developability challenge, namely phys. instability limiting extended shelf life. Using orthogonal characterization methods, we identify the mechanism of LNP instability as Ostwald ripening and establish it to be driven predominantly by the asym. amino lipid component. Through rational optimization of LNP phys. and macromol. properties, we are able to significantly attenuate or entirely eliminate the Ostwald ripening instability. Modulation of LNP size, for example, effectively halts particle growth. Similarly, optimization of LNP macromol. packing through deliberate selection of structurally matched colipids significantly diminishes the rate of ripening. This later exptl. observation is substantiated by mol. dynamics simulations of LNP self-assembly, which establish a quant. dependence of LNP macromol. order on colipid structure. In totality, the exptl. and mol. dynamics outcomes of this work support the rational design of LNP phys. and chem. properties leading to effective Ostwald ripening stabilization and enable the advance of asym. LNPs as a clinic-ready platform for siRNA therapeutics. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Application of 1224606-06-7).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Acyl chlorides and acid anhydrides alcoholysis is another way to produce esters. Acyl chlorides and acid anhydrides react with alcohols to produce esters. Anydrous conditions are recommended since both acyl chlorides and acid anhydrides react with water.Application of 1224606-06-7

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Juang, Lih Jiin et al. published their research in Blood in 2022 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Suppression of fibrin(ogen)-driven pathologies in disease models through controlled knockdown by lipid nanoparticle delivery of siRNA was written by Juang, Lih Jiin;Hur, Woosuk S.;Silva, Lakmali M.;Strilchuk, Amy W.;Francisco, Brenton;Leung, Jerry;Robertson, Madelaine K.;Groeneveld, Dafna J.;La Prairie, Bridget;Chun, Elizabeth M.;Cap, Andrew P.;Luyendyk, James P.;Palumbo, Joseph S.;Cullis, Pieter R.;Bugge, Thomas H.;Flick, Matthew J.;Kastrup, Christian J.. And the article was included in Blood in 2022.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate The following contents are mentioned in the article:

Fibrinogen plays a pathol. role in multiple diseases. It contributes to thrombosis and modifies inflammatory and immune responses, supported by studies in mice expressing fibrinogen variants with altered function or with a germline fibrinogen deficiency. However, therapeutic strategies to safely and effectively tailor plasma fibrinogen concentration are lacking. Here, we developed a strategy to tune fibrinogen expression by administering lipid nanoparticle (LNP)-encapsulated small interfering RNA (siRNA) targeting the fibrinogen 伪 chain (siFga). Three distinct LNP-siFga reagents reduced both hepatic Fga mRNA and fibrinogen levels in platelets and plasma, with plasma levels decreased to 42%, 16%, and 4% of normal within 1 wk of administration. Using the most potent siFga, circulating fibrinogen was controllably decreased to 32%, 14%, and 5% of baseline with 0.5, 1.0, and 2.0 mg/kg doses, resp. Whole blood from mice treated with siFga formed clots with significantly decreased clot strength ex vivo, but siFga treatment did not compromise hemostasis following saphenous vein puncture or tail transection. In an endotoxemia model, siFga suppressed the acute phase response and decreased plasma fibrinogen, D-dimer, and proinflammatory cytokine levels. In a sterile peritonitis model, siFga restored normal macrophage migration in plasminogen-deficient mice. Finally, treatment of mice with siFga decreased the metastatic potential of tumor cells in a manner comparable to that observed in fibrinogen-deficient mice. The results indicate that siFga causes robust and controllable depletion of fibrinogen and provides the proof-of-concept that this strategy can modulate the pleiotropic effects of fibrinogen in relevant disease models. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Cohen, Zvi R. et al. published their research in ACS Nano in 2015 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Reference of 1224606-06-7

Localized RNAi Therapeutics of Chemoresistant Grade IV Glioma Using Hyaluronan-Grafted Lipid-Based Nanoparticles was written by Cohen, Zvi R.;Ramishetti, Srinivas;Peshes-Yaloz, Naama;Goldsmith, Meir;Wohl, Anton;Zibly, Zion;Peer, Dan. And the article was included in ACS Nano in 2015.Reference of 1224606-06-7 The following contents are mentioned in the article:

Glioblastoma multiforme (GBM) is one of the most infiltrating, aggressive, and poorly treated brain tumors. Progress in genomics and proteomics has paved the way for identifying potential therapeutic targets for treating GBM, yet the vast majority of these leading drug candidates for the treatment of GBM are ineffective, mainly due to restricted passages across the blood-brain barrier. Nanoparticles have been emerged as a promising platform to treat different types of tumors due to their ability to transport drugs to target sites while minimizing adverse effects. Herein, we devised a localized strategy to deliver RNA interference (RNAi) directly to the GBM site using hyaluronan (HA)-grafted lipid-based nanoparticles (LNPs). These LNPs having an ionized lipid were previously shown to be highly effective in delivering small interfering RNAs (siRNAs) into various cell types. LNP’s surface was functionalized with hyaluronan (HA), a naturally occurring glycosaminoglycan that specifically binds the CD44 receptor expressed on GBM cells. We found that HA-LNPs can successfully bind to GBM cell lines and primary neurosphers of GBM patients. HA-LNPs loaded with Polo-Like Kinase 1 (PLK1) siRNAs (siPLK1) dramatically reduced the expression of PLK1 mRNA and cumulated in cell death even under shear flow that simulate the flow of the cerebrospinal fluid compared with control groups. Next, a human GBM U87MG orthotopic xenograft model was established by intracranial injection of U87MG cells into nude mice. Convection of Cy3-siRNA entrapped in HA-LNPs was performed, and specific Cy3 uptake was observed in U87MG cells. Moreover, convection of siPLK1 entrapped in HA-LNPs reduced mRNA levels by more than 80% and significantly prolonged survival of treated mice in the orthotopic model. Taken together, our results suggest that RNAi therapeutics could effectively be delivered in a localized manner with HA-coated LNPs and ultimately may become a therapeutic modality for GBM. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Reference of 1224606-06-7).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Reference of 1224606-06-7

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Park, Soohyung et al. published their research in Journal of Chemical Information and Modeling in 2021 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Related Products of 1224606-06-7

CHARMM-GUI Membrane Builder for Lipid Nanoparticles with Ionizable Cationic Lipids and PEGylated Lipids was written by Park, Soohyung;Choi, Yeol Kyo;Kim, Seonghoon;Lee, Jumin;Im, Wonpil. And the article was included in Journal of Chemical Information and Modeling in 2021.Related Products of 1224606-06-7 The following contents are mentioned in the article:

A lipid nanoparticle (LNP) formulation is a state-of-the-art delivery system for genetic drugs such as DNA, mRNA, and small interfering RNA, which is successfully applied to COVID-19 vaccines and gains tremendous interest in therapeutic applications. Despite its importance, a mol.-level understanding of the LNP structures and dynamics is still lacking, which makes rational LNP design almost impossible. In this work, we present an extension of CHARMM-GUI Membrane Builder to model and simulate all-atom LNPs with various (ionizable) cationic lipids and PEGylated lipids (PEG-lipids). These new lipid types can be mixed with any existing lipid types with or without a biomol. of interest, and the generated systems can be simulated using various mol. dynamics engines. As a first illustration, we considered model LNP membranes with DLin-KC2-DMA (KC2) or DLin-MC3-DMA (MC3) without PEG-lipids. The results from these model membranes are consistent with those from the two previous studies, albeit with mild accumulation of neutral MC3 in the bilayer center. To demonstrate Membrane Builder’s capability of building a realistic LNP patch, we generated KC2- or MC3-containing LNP membranes with high concentrations of cholesterol and ionizable cationic lipids together with 2 mol % PEG-lipids. We observe that PEG-chains are flexible, which can be more preferentially extended laterally in the presence of cationic lipids due to the attractive interactions between their head groups and PEG oxygen. The presence of PEG-lipids also relaxes the lateral packing in LNP membranes, and the area compressibility modulus (KA) of LNP membranes with cationic lipids fit into typical KA of fluid-phase membranes. Interestingly, the interactions between PEG oxygen and the head group of ionizable cationic lipids induce a neg. curvature. We hope that this LNP capability in Membrane Builder can be useful to better characterize various LNPs with or without genetic drugs for rational LNP design. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Related Products of 1224606-06-7).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Related Products of 1224606-06-7

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zimmermann, Christoph M. et al. published their research in Journal of Controlled Release in 2022 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.Recommanded Product: (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery was written by Zimmermann, Christoph M.;Baldassi, Domizia;Chan, Karen;Adams, Nathan B. P.;Neumann, Alina;Porras-Gonzalez, Diana Leidy;Wei, Xin;Kneidinger, Nikolaus;Stoleriu, Mircea Gabriel;Burgstaller, Gerald;Witzigmann, Dominik;Luciani, Paola;Merkel, Olivia M.. And the article was included in Journal of Controlled Release in 2022.Recommanded Product: (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate The following contents are mentioned in the article:

While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to phys., chem. and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders. Spray drying was performed using 5% lactose solution (m/V), and the targets were set to obtain nanoparticle sizes after redispersion of spray-dried powders around 150 nm, a residual moisture level below 5%, and RNA loss below 15% at maintained RNA bioactivity. The LNPs consisted of an ionizable cationic lipid which is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG encapsulating siRNA. Prior to the spray drying, the latter process was simulated with a novel dual emission fluorescence spectroscopy method to preselect the highest possible drying temperature and excipient solution maintaining LNP integrity and stability. Through characterization of physicochem. and aerodynamic properties of the spray dried powders, administration criteria for delivery to the lower respiratory tract were fulfilled. Spray dried LNPs penetrated the lung mucus layer and maintained bioactivity for >90% protein downregulation with a confirmed safety profile in a lung adenocarcinoma cell line. Addnl., the spray dried LNPs successfully achieved up to 50% gene silencing of the house keeping gene GAPDH in ex vivo human precision-cut lung slices at without increasing cytokine levels. This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Recommanded Product: (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.Recommanded Product: (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Forster, James III et al. published their research in Biomaterials Science in 2022 | CAS: 1224606-06-7

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

mRNA-carrying lipid nanoparticles that induce lysosomal rupture activate NLRP3 inflammasome and reduce mRNA transfection efficiency was written by Forster, James III;Nandi, Dipika;Kulkarni, Ashish. And the article was included in Biomaterials Science in 2022.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate The following contents are mentioned in the article:

In the last several years, countless developments have been made to engineer more efficient and potent mRNA lipid nanoparticle vaccines, culminating in the rapid development of effective mRNA vaccines against COVID-19. However, despite these advancements and materials approaches, there is still a lack of understanding of the resultant immunogenicity of mRNA lipid nanoparticles. Therefore, a more mechanistic, design-driven approach needs to be taken to determine which biophys. characteristics, especially related to changes in lipid compositions, drive nanoparticle immunogenicity. Here, we synthesized a panel of six mRNA lipid nanoparticle formulations, varying the concentrations of different lipid components and systematically studied their effect on NLRP3 inflammasome activation; a key intracellular protein complex that controls various inflammatory responses. Initial experiments aimed to determine differences in nanoparticle activation of NLRP3 inflammasomes by IL-1尾 ELISA, which unveiled that nanoparticles with high concentrations of ionizable lipid DLin-MC3-DMA in tandem with high cationic lipid DPTAP and low cholesterol concentration induced the greatest activation of the NLRP3 inflammasome. These results were further corroborated by the measurement of ASC specks indicative of NLRP3 complex assembly, as well as cleaved gasdermin-D and caspase-1 expression indicating complex activation. We also uncovered these activation profiles to be mechanistically correlated primarily with lysosomal rupturing caused by the delayed membrane disruption capabilities of ionizable lipids until the lysosomal stage, as well as by mitochondrial reactive oxygen species (ROS) production and calcium influx for some of the particles. Therefore, we report that the specific, combined effects of each lipid type, most notably ionizable, cationic lipids, and cholesterol, is a crucial mRNA lipid nanoparticle characteristic that varies the endo/lysosomal rupture capabilities of the formulation and activate NLRP3 inflammasomes in a lysosomal rupture dependent manner. These results provide a more concrete understanding of mRNA lipid Nanoparticle-Associated Mol. Patterns for the activation of mol.-level immune responses and provide new lipid composition design considerations for future mRNA-delivery approaches. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate).

(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Safety of (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics