ACS Omega. 2018 Feb 28;3(2):2396-2405. doi: 10.1021/acsomega.7b02022. Epub 2018 Feb 27. Combined Adsorption and Covalent Linking of Paclitaxel on Functionalized Nano-Graphene Oxide for Inhibiting Cancer Cells Wei Zhuang, Linjiao He, Kai Wang, Bo Ma, Lei Ge, Zhenfu Wang, Jinsha Huang, Jinglan Wu, Qi Zhang, Hanjie Ying Abstract Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency. Related products Abbreviation: 4-arm PEG-NH2 Name: 4-arm Poly(ethylene glycol) amine For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Langmuir. 2020 Feb 11;36(5):1235-1240. doi: 10.1021/acs.langmuir.9b03325. Epub 2020 Jan 27. Host-Guest Interactions between Oxaliplatin and Cucurbit[7]uril/Cucurbit[7]uril Derivatives under Pseudo-Physiological Conditions Han Wu, Hao Chen, Bohan Tang, Yuetong Kang, Jiang-Fei Xu, Xi Zhang Abstract Compared with conventional drug delivery systems (DDSs), DDSs based on host-guest interactions possess unique advantages, such as high selectivity, tunable binding ability, and controllable release of drugs. It is important to study the host-guest interactions between the carrier and drug under physiological conditions for constructing DDSs. In this work, we have studied the host-guest interaction between cucurbit[7]uril (CB[7]) and oxaliplatin (OxPt), a clinical antitumor drug, in the cell culture medium. The results show that amino acids such as phenylalanine in the 1640 culture medium can partially occupy the cavity of CB[7], which leads to the decrease of enthalpy changes of the host-guest interaction between OxPt and CB[7]. In addition, inorganic salts such as NaCl in the medium reduce the enthalpy change and increase the entropy change of the binding because of the preorganization of the portal of CB[7] and sodium cation. As a result, the binding constant of CB[7] with OxPt in the 1640 culture medium is 1/20 of that in pure water. When CB[7] is modified at the terminal of star-type PEG to construct the star-PEGylated CB[7], it is shown that the molecular weight and topological structure of the PEG polymer backbone exhibit little effect on the host-guest interactions between CB[7] and OxPt. This study enriches the host-guest chemistry of cucurbiturils and may provide guidance for constructing novel DDSs based on host-guest interactions with high loading and releasing efficiency. Related products Abbreviation: 2-arm PEG-N3 (PT02) Name: 2-arm Methoxypoly (ethylene glycol) azide (PT02) For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

LNP formulations usually have between 35-45% composition with respect to cholesterol. Cholesterol is a derivative of cyclopentane polyhydrophenanthrene, which is widely present in animals. Cholesterol is involved in the formation of cell membranes and is an indispensable and important substance in animal tissue cells. Traditionally, cholesterol is derived from animals, mainly from the saponification of the brain and vertebral tendons of pigs, cattle and sheep, or lanolin, which is extracted using organic solvents. Since many diseases are now found to be transmitted from animals to humans, according to the latest guidelines for cell therapy and gene therapy, animal-derived ingredients should be avoided and a safer source of cholesterol is needed. SINOPEG's plant-derived cholesterol is synthesized through biosynthesis technology using plant extracts as the initial raw material. The product has no animal origin and meets the guidelines for cell therapy and gene therapy with high safety and clear composition. The product is a pure plant-derived biosynthetic cholesterol with no animal-derived components. It is less risky compared to traditional lanolin, pig, and cow products of animal origin. Plant-derived cholesterol is well suited for applications in the preparation of lipid nanoparticle (LNP) delivery systems, in the development of mRNA vaccines, in cell culture, serum-free cell culture for protein drugs, and other high-technology drug researches. Plant-derived cholesterol can also be used as a key raw material for the synthesis of vitamin D and its derivatives. The typical application includes such as in small unilamellar vesicles’ preparation, in the preparation of small unilamellar vesicles for structured illumination microscopy studies, in the generation of thymoquinone (TQ) loaded liposomes for administering into murine model with Candida albicans infection. Lipids for LNPs DHA (ALC-0315) mPEG-DTA (ALC-0159) HUO (SM-102) mPEG-DMG DSPC DOPE Cholesterol (Plant) R-DODMA R-DOTMA-Cl Dlin-MC3-DMA DOTAP DOTAP-Cl mPEG-DSG mPEG-C-DMG DSPE-PEG-MAL For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Cell & Gene Therapy Bioprocessing & Commercialization is the most focused event for cost effective and efficient cell, gene and immunotherapy approaches. CGT delivers the focused science and business content designed specifically for the cell therapy and regenerative medicine fields, while providing a pivotal gathering place for connecting industry, funding sources, government and academia. Welcome to visit us at SINOPEG's Booth#104at CGT, Boston Convention and Exhibition Center, USA from 27th to 30th September. https://informaconnect.com/cell-therapy-bioprocessing/ #event #CGT #Boston SINOPEG is a dynamic science company with professional R&D, Manufacturing and Sales capability. The company is mainly engaged in drug delivery system (DDS) and new medical materials business. Founded in 2011, SINOPEG has a team of highly qualified and science background employee personnel. We devote ourselves to research, develop and produce high quality Polyethylene glycol, Polyethylene glycol derivatives, Block copolymers, Anti-diabetic drug side chains, lipids for LNPs, GalNAc conjugates, ADC and ProTAC Linker, etc. Please contact us at sales@sinopeg.com 

#ASOs #antisense oligonucleotide #GalNAc #drug delivery #ligand targeting   Drug development scheme using the GalNAc conjugate, is better suited for selecting BNA-based ASOs, especially for the treatment of liver-associated diseases.   gnitude   https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(22)00428-2   Antisense oligonucleotides (ASOs) containing bridged nucleic acids (BNAs) have been proven to be very powerful. However, there is still a challenge to ensure a reliable discovery and translational development scheme for this class of ASOs with wider therapeutic windows. The robustness of the scheme was demonstrated in the context of the selection of ASOs, which have two different BNA chemistries (2,′4′-BNA/locked nucleic acid [LNA] and amido-bridged nucleic acid [AmNA]) targeting human proprotein convertase subtilisin/kexin type 9 (PCSK9). A two-step process was shemed, including a unique and sensitive in vitro screening approach, called Ca2+ enrichment of medium (CEM) transfection, and a ligand-targeted drug delivery approach to better reach target tissues, averting unintended accumulation of ASOs. An N-acetylgalactosamine (GalNAc) ligand then was appended to the candidate ASO to further broaden the therapeutic margin by altering the molecule’s pharmacokinetics. With reduced nephrotoxicity in rats, the GalNAc conjugate, HsPCSK9-1811-LNA, was found to be at least ten times more potent in non-human primates. Overall, a drug development scheme was shown better suited for selecting clinically relevant BNA-based ASOs, especially for the treatment of liver-associated diseases.

Bagsværd, Denmark , 2 2 August 2022 – Novo Nordisk today announced headline results from a phase 2 clinical trial with CagriSema, a once-weekly subcutaneous combination of semaglutide and a novel amylin analogue, cagrilintide. The trial investigated the efficacy and safety of a fixed dose combination of CagriSema (2.4 mg semaglutide and 2.4 mg cagrilintide) compared to the individual components semaglutide 2.4 mg and cagrilintide 2.4 mg, all administered once weekly, in 92 people with type 2 diabetes and overweight. People were equally randomised among the three treatment arms. In the trial, the mean baseline HbA1c was 8.4% and the mean baseline body weight was 106 kg. After 32 weeks of treatment, people treated with CagriSema achieved a numerically higher HbA1c reduction of 2.18%-points compared to a reduction of 1.79%-points for people treated with semaglutide and 0.93%-points with cagrilintide alone. People treated with CagriSema achieved a numerically higher body weight reduction of 15.6% compared to a reduction of 5.1% for people treated with semaglutide and 8.1% with cagrilintide alone1. In the trial, CagriSema appeared to have a safe and well-tolerated profile. “We are encouraged by the impressive phase 2 results for CagriSema in people with type 2 diabetes,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “The results indicate that CagriSema reduces blood sugar more than semaglutide alone and the weight loss seen in the trial confirms the substantial weight lowering potential of CagriSema”. Based on the results, Novo Nordisk is now planning to initiate a phase 3 development programme for CagriSema in people with type 2 diabetes in 2023. The CagriSema (2.4 mg semaglutide and 2.4 mg cagrilintide) phase 3 programme in people with overweight and obesity, REDEFINE, is expected to begin in the fourth quarter of 2022. Source:  https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=131155

Nearly half of all vaccines go to waste due to the strict temperature regulation needed throughout the manufacturing process and vaccine administration, meaning they need to be refrigerated to remain effective. To mitigate this, researchers from ETH Zurich (Germany) in collaboration with Nanoly Bioscience (CO, USA) have developed a new hydrogel to package vaccines and increase their thermal stability.   The hydrogel is based on a biocompatible synthetic polymer, polyethylene glycol (PEG), that acts like a molecular Tupperware, keeping large complex molecules separated from each other, like the proteins found in vaccines, antibodies and gene therapies.   In vaccines, the PEG-based hydrogel encapsulates proteins enabling them to withstand a higher range of temperature fluctuations by preventing them from aggregating together. Without the packaging, cold chain vaccines tend to withstand a temperature range of 2°C – 8°C (35°F – 45°F). With this reversible packaging system, the temperature range is increased to 25°C – 65°C (75°F – 150°F).   The hydrogel capitalizes on dynamic covalent bonds, creating a reversible platform that can easily release the proteins from their Tupperware box by adding a simple sugar solution. This means vaccines can be easily recovered at their point of use.     The PEG-based hydrogel could yield economic benefits by reducing the costs and health risks that are associated with cold supply chains and mean more funding can be put towards the production of vaccines.     Before this molecular Tupperware can be rolled out, safety studies and clinical trials are needed. Until then, the technology could be used in a variety of ways including transporting heat-sensitive enzymes used in cancer research or protein molecules in research lab settings.     Source:https://www.biotechniques.com/bioengineering-biophysics/increasing-vaccine-thermal-stability-with-peg-based-hydrogels/

– Patisiran Met the Primary Endpoint with a Statistically Significant Improvement in 6-Minute Walk Test Compared to Placebo at 12 Months – – Patisiran Also Met the First Secondary Endpoint with a Statistically Significant Improvement in Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire, Compared to Placebo at 12 Months – – Patisiran Demonstrated Encouraging Safety and Tolerability Profile in Patients with ATTR Amyloidosis with Cardiomyopathy – – Company Plans to File a Supplemental New Drug Application in U.S. in Late 2022 – – Full Data Will Be Presented at the 18th International Symposium on Amyloidosis – – Alnylam to Host Conference Call Today at 8:00 am ET – August 03, 2022 07:00 AM Eastern Daylight Time CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the APOLLO-B Phase 3 study of patisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, met the primary endpoint of change from baseline in the 6-Minute Walk Test (6-MWT) at 12 months compared to placebo (p-value 0.0162). The study also met the first secondary endpoint of change from baseline in quality of life compared to placebo, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (p-value 0.0397). “We are thrilled that APOLLO-B successfully met all its major objectives, which we believe for the first time validates the hypothesis that TTR silencing by an RNAi therapeutic can be an effective approach for treating the cardiomyopathy of ATTR amyloidosis” Tweet this The study also included additional secondary composite outcome endpoints to be tested in a hierarchical manner. A non-significant result (p-value 0.0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months compared to placebo. As a result, formal statistical testing was not performed on the final two composite endpoints, which were not powered for statistical significance given the short duration of the study — all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (nominal p-value 0.9888), and in the overall population (nominal p-value 0.5609). Patisiran also demonstrated an encouraging safety and tolerability profile, with deaths numerically favoring the patisiran arm. “We are thrilled that APOLLO-B successfully met all its major objectives, which we believe for the first time validates the hypothesis that TTR silencing by an RNAi therapeutic can be an effective approach for treating the cardiomyopathy of ATTR amyloidosis,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure, affecting greater than 250,000 patients around the world. Thes...