LNP delivery system The major COVID-19 vaccine technology routes currently under development worldwide include inactivated vaccines, mRNA vaccines, adenovirus vaccines and recombinant protein vaccines. As a new vaccine technology in the market, mRNA vaccine is also one of the most important COVID-19 vaccines in the world at present. As a new technology, why can mRNA vaccine be widely administered around the world? One important reason is that it has a very high effective protection rate. The two available mRNA vaccines have an effective protection rate of more than 90%, and BioNTech's mRNA vaccine, produced in collaboration with Pfizer, has an effective protection rate of 95%.Since vaccination began, the daily positive rate in the United States has dropped from 20 percent to 1 to 2 percent. MRNA transmits the genetic information for producing an antigen to the cells that make the protein. These cells then present the antigen to their surfaces, triggering the specific immune response needed. Eventually, when a virus invades, the immune system recognizes specific antigens and quickly and specifically attacks the virus to prevent infection. MRNA technology can not only be used as a preventive vaccine to prevent the spread of infectious diseases, but also as a therapeutic drug to treat some serious diseases, such as cancer and AIDS, due to its ability to spontaneously stimulate human immunity. MRNA has large molecular weight, strong hydrophilicity and high biological activity, but its single chain structure makes it extremely unstable and easy to be degraded, and delivery through the membrane with negative charge on the surface is also difficult. MRNA must enter the cell to encode antibodies, and the enzyme degradation and cell membrane barrier in the process of entering the cell are the biggest challenges that affect its delivery efficiency and transfection efficiency. Special modification or package delivery systems are required to achieve intracellular expression of mRNA. At present, Lipid nanoparticle (LNP) is commonly used as a carrier to deliver mRNA .Lipid nanoparticles mainly contain four components: ionizable lipids, neutral helper lipids, cholesterol, and PEGylated lipid. The neutral helper lipids are usually saturated phospholipids, which support the formation of the lamellar lipid bilayer and stabilize its structure arrangement. Cholesterol had strong membrane fusion, which promoted the intracellular uptake of mRNA and cytoplasmic entry. Pegylated lipids are located on the surface of lipid nanoparticles, improving their hydrophilicity and avoiding rapid removal by the immune system, preventing particle aggregation and increasing stability. The most critical excipients are ionizable cationic lipids, which are decisive factors in the efficiency of mRNA delivery and transfection. Mechanism of LNP mRNA delivery: before entering cells, cationic lipids can realize electrostatic complexation with negatively charged mRNA molecules to form complex...

Lipid nanoparticles (LNP) can play an important role in gene editing therapy. IntelliaTherapeutics and Regeneron recently announced that their co-development program, ntra-2001, a systemic CRISPR/Cas9 therapy, has achieved positive results in a phase I clinical trial. A single dose of NTLA2001 resulted in an average 87% decrease in serum transthyroxine protein level (TTR), with a maximum reduction of 96% at day 28.CRISPR/Cas9 is a gene-editing tool that makes permanent, precisely targeted changes to a patient's chromosome and fixes potential genetic mutations.Ntra-2001 is a CRISPR/ CAS9-based treatment for hereditary transthyroxine protein-mediated amyloidosis with polyneuropathy (ATTRV-PN). According to Intellia Therapeutics, NTRA-2001 is a targeted delivery of LNP in humans that selectively knocks out disease-causing genes and restores necessary genetic function through targeted insertion. Three of the six patients treated in the Phase I trial received a dose of 0.1mg/kg ntLA-2001 and the other three received a dose of 0.3mg/kg NTLA2001.At day 28, TTR decreased by an average of 52% in patients receiving 0.1mg/kg and 87% in patients receiving 0.3mg/kg, with a 97% reduction in one patient. As revealed in IntelliaTherapeutics' patent, LNP contains amine lipids for encapsulation and in vivo escape, neutral and helper lipids for stabilization, and cloaking lipids. In general, LNPS used on CRISPR/Cas9 include DSPC, cholesterol, PE2K-DMG and other liposomes, which are mostly similar to those used for LNPS of mRNA vaccines. XIAMEN SINOPEG BIOTECH CO., LTD. has been developing DDS sustained-release system for more than ten years, and has strong technical reserves and experienced quality team. The high-quality polyethylene glycol derivatives developed and produced by the company have been successfully applied in the long-acting modification of PEG proteins, peptides and three types of medical devices. We also supply high purity fatty acid side chain to the market for peptide modification. In recent years, SINOPEG has turned to polyethylene glycol phospholipid, polyethylene glycol block copolymer and other high-end complex preparations, and has carried out a number of projects with domestic leading pharmaceutical enterprises. Interested friends can contact us through the following ways: US Tel: 1-844-782-5734 CHN Tel: 400-918-9898 Email: sales@sinopeg.com Reference 1. Intellia Therapeutics. (2021).Source: retrieve Intellia Therapeutics: https://www.intelliatx.com/crisprcas9/types-of-edits-2/ 2.IntelliaTherapeutics(NTLA.us) and Regentium (RegN.us) announce the results of the first CRISPR clinical trial.Retrieve source: baidu: https://baijiahao.baidu.com/s?id=1703680441595581467&wfr=spider&for=pc

Despite the three-dimensional structure of tissues in vivo, the researches on the structures, functions and pathology of human tissues frequently relies on the two-dimensional (2D) model in vitro and animal model. Since the structure of monolayer in vitro model is quite different from the cell microenvironment in vivo, cell behaviors and functions, such as cell–cell interaction and cell-matrix interaction, are greatly affected. Moreover, animal model often fail to repeat the human characteristic because of species differences. Three-dimensional (3D) culture of tumor cell lines has been advocated as the alternative. It is simple and practicable and has the advantage of simulating the cell microenvironment in vivo. Matrices for 3D cell culture mimic one or more properties of the extracellular matrix (ECM) and tumor microenvironment in vivo. The 3D cell culturing matrices are generally composed of porous structures with diameter less than 300 nm, which can provide enough space for the growth of cells. The cancer cells can form 3D aggregates or spheroids inside the matrix. According to the main component, 3D cell culture matrices can be divided into two main categories: matrix based on natural materials and matrix based on synthetic materials. Matrices based on natural materials can provide a biological environment, but the mechanical performance of materials is commonly poor and the batch-to-batch discrepancy cannot be completely eliminated. Natural materials are usually used to form hydrogel composites. Synthetic scaffolds are polymers like Polyethylene glycol (PEG), Polylactide (PLA), Poly(lactide-co-glycolide) (PLGA/PLG) which are biodegradable and easy to reproduce. Among these materials, the thermogelling synthetic copolymer hydrogels with a sol-gel transition exhibit lower critical solution temperature (LCST) behavior, which is meaningful for a 3D cell culturing matrix. When the sol gel transition temperature of smart hydrogel is between 5℃ and 37℃, the matrix has advantages in further separation of materials and cell aggregates. Hydrogels have received extensive attention in tissue engineering and 3D cell culture, owing to their inherent properties such as flexible matrix, high water content, and responsive network structures. Hydrogels can be formed both chemically and physically. PEG hydrogels are excellent candidates as biomaterials because of their potential for incorporating both biophysical and biochemical cues and their prevention of non-specific protein adsorption, biocompatibility and FDA approval for use in humans. Thermo-sensitive hydrogel based on PLGA-PEG-PLGA tri-block copolymers has been used for delivery of proteins and water-insoluble drugs. The proper LCST and good biocompatibility of PLGA-PEG-PLGA tri-block copolymers make it a good choice for in vitro cell culture matrix. References 1. Caldwell A. S., Aguado B. A., Anseth K. S. Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments. Adv Fu...

Cancer remains one of the most common diseases that is a threat to human health. Currently, chemotherapy is an important and indispensable strategy for treating cancer besides surgical treatment and radiotherapy. Thus, it has attracted a number of pharmaceutical researchers for the discovery and development of new anticancer drugs. Unfortunately, approximately 90% of drug candidate molecules in the discovery pipeline are poorly water soluble. Poor solubility can elicit low oral bioavailability and insufficient efficacy in vivo, and make intravenous (IV) administration challenging. Nanotechnology-based drug delivery systems, such as drug nanocrystals (NCs) and liposomes have enabled in improving the solubility and/or attained targeted delivery via the enhanced permeability and retention (EPR) effect, and/or specific ligand-mediated tumor-targeting effect. Liposome is one of the most developed nanomedicines, high stability and flexible surface modification/functionalization, have been widely used in the field of drug development. Hydrophobic drugs are mainly entrapped in the liposomes by embedding in the lipid bilayers, which usually results in a low drug loading capacity that challenges their clinical transformation. In contrast, drug NCs, a nanoscale carrier-free colloidal delivery system with a theoretical drug loading capacity of up to 100%, are quite promising for poorly water-soluble drugs. However, drug NCs still face major challenges in their stability and targeted delivery. Recently, researchers from the Chinese Academy of Sciences present a novel drug delivery strategy, called nanocrystal@liposome (NC@Lipo), which integrates drug nanocrystals into the hydrophilic inner cores of liposomes and forms a hybrid core (nanocrystal)-shell (liposome) drug delivery system, merging the advantages of liposomes and drug nanocrystals to overcome these issues，for the targeted delivery of poorly watersoluble drugs. The performance of the proposed NC@Lipo delivery system was demonstrated on the drug candidate CHMFL-ABL-053 (053), which was discovered by their group. Three different 053-nanodrugs, namely 053-NC, 053-NC@PEG-Lipo, and 053-NC@FA-Lipo, were fabricated for in vitro and in vivo evaluation. In conclusion, as a proof of concept, this study showed that NC@Lipo might be a potential strategy for designing nanocrystal or liposome-based drug delivery systems with high colloidal stability, high drug loading, functionalized surface, and enhanced biological effects (including PK profile, tumor cell targeting, and in vivo antitumor efficacy). Additionally, this work may promote the development of more efficient liposome-based formulations for the delivery of poorly water-soluble drugs for commercial and clinical applications. 1. Title：Nanocrystal-loaded liposome for targeted delivery of poorly water-soluble antitumor drugs with high drug loading and stability towards efficient cancer therapy 2. Author: Huamin Liang, Fengming Zou, Qingwang Liu, Beilei Wang,...

Drug excipients not only have an effect on the manufacturing process of the drug, but also have an important influence on whether the drug has the desired effect in the human body. As the COVID-19 epidemic continues to spread around the world, coverage for COVID-19 vaccination is critical. Specific excipients play an important role in making vaccines more effective. What are the characteristics of supplying good quality COVID-19 excipients?   1. High safety performance   The main function of drugs is to cure diseases. If drug excipients as additives are used without safety evaluation, they may cause harm to human body. Especially for COVID-19 vaccine, which has not been on the market for a long time, the safety of excipients should be considered as a top priority. Therefore, to evaluate the safety of COVID-19 excipients, suppliers are required to provide safety assessment reports.   2. The performance of auxiliary materials is stable and effective   Because the COVID-19 vaccine has a wide range of injection, involves all age groups and varies in body quality, the effect of the vaccine will be greatly reduced if the stable performance of exciphants cannot be guaranteed, which is extremely detrimental to our efforts to contain the spread of COVID-19. Therefore, the performance stability should be taken as one of the key factors to evaluate whether a vaccine excipient is of good quality.   3. Strong supply capacity   At present, countries around the world are actively purchasing the new coronavirus from multiple sources, and the public are encouraged to receive the vaccine without charging for the publicity. However, the supply of vaccine production companies is still in short supply, which shows the huge demand for vaccine. Therefore, a good vaccine excipient supplier should have sufficient supply capacity to ensure that there is no shortage of product supply and can better meet the needs of vaccine manufacturers.   In conclusion, the new crown vaccine supply good quality materials with high safety performance, stable performance, effective, strong supply capacity, and other key factors, the new crown vaccine manufacturers can distinguish from the above aspects, after screening before the relevant preparatory work, so that can ensure the quality of produce vaccines have security, security hidden danger.   SINOPEG can provide high quality covid-19 vaccine excipients. Welcome to contact us.  research use only.

Osteoporosis is defined as a systemic and metabolic bone disease, which is characterized by a decrease in bone mass per unit volume and deterioration of the microstructure of bone tissue, thereby increasing bone fragility and susceptibility to fracture. With the increase in the proportion of elderly populations in the world, and in consequence the number of postmenopausal woman, sarcopenia and osteoporosis are important public health issues. Alendronate (ALN) is a kind of bisphosphonate, which is the most widely used medication in the treatment of skeletal disorders such as osteoporosis, due to its significant pharmacological effect of inhibition on bone resorption. However, the poor permeability exhibit extremely low bioavailability after oral administration (less than 1%). Furthermore, to avoid serious side effects caused by drug-food interactions, patients were instructed to take the medication orally in the morning at least 30 min before breakfast with abundant water and on an empty stomach after an overnight fast, and to remain upright for at least 30 min after dosing. To overcome the limitations of conventional treatments and provide better patient compliance, researchers from the Chinese Academy of Sciences and Zhengzhou University have jointly developed a minimally invasive procedures system for long-term injectable drug delivery, which is effective for clinical osteoporosis therapy (Scheme 1). They introduced PEGylated ALN (PEG-ALN) prodrug into the tetra-PEG hydrogel network, which limits the release rate of ALN because the PEG-ALN polymer does not move easily and freely in the 4 arm PEG hydrogel network, thus achieving slow drug release and local drug delivery, avoiding the serious side effects of systemic administration. 1. Dawei Li, Jin Zhou, Mingming Zhang, Yuanzheng Ma, Yanyu Yang,* Xue Han* and Xing Wang*. Long-term delivery of alendronate through injectable tetra-PEG hydrogel to promote osteoporosis therapy. Biomater. Sci. 2020, 8, 3138–3146.

Both frontrunner companies, Moderna and Pfizer-BioNTech, encapsulated their mRNA vaccines using lipid nanoparticles (LNPs) to protect the mRNA from nuclease degradation. LNPs is one of the most advanced delivery systems and has proven to be safe and effective in siRNA delivery. LNP formulations are typically composed of an ionizable lipid, cholesterol, lipid conjugated with polyethylene glycol (PEGylated lipid) and a helper lipid, have recently been recognized as a novel delivery system, and the use of PEG enhances the stability and longevity of the lipid nanoparticles. The mechanism of LNP-mediated delivery of mRNA is not fully understood, but LNPs are suggested to be internalized by endocytosis and are attached electrostatically and fused with the cell membrane via inverted non-bilayer lipid phases. Interestingly, LNPs can also be excreted out of cells by exocytosis，which is a point to note for mRNA delivery via LNPs. Systemically delivered mRNA-LNP complexes mainly target the liver owing to binding of apolipoprotein E and subsequent receptor-mediated uptake by hepatocytes. These microscopic oil-like droplets, approximately 0.1 μm in diameter, surround and protect the fragile mRNA during production, transport, and eventual injection into the body. On the other hand, nanoparticles as vaccine delivery systems can enhance antigen delivery to the target tissue and cell populations of interest, and act as immunostimulatory adjuvants to activate or augment specific immune responses. PEG has never been found in any other vaccine in the world, and this will be another new use of PEG in the pharmaceutical field. SINOPEG is Covid-19 Vaccine Excipients supplier.  research use only

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