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Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs
Drug Metab Pharmacokinet. 2021 Oct 10;41:100424. doi: 10.1016/j.dmpk.2021.100424. Online ahead of print.ABSTRACTNucleic acid therapeutics are developing into precise medicines that can manipulate specific genes. However, the development of safe and effective delivery system for the target cells has remained a challenge. Lipid nanoparticles (LNPs) have provided a revolutionary delivery system that can ensure multiple clinical translation of RNA-based candidates. In 2018, Patisiran (Onpattro) was first approved as an LNP-based siRNA drug. In 2020, during the coronavirus disease 2019 (COVID-19) outbreak, LNPs have enabled the...
Source: Drug Metabolism and Pharmacokinetics - November 10, 2021 Category: Drugs & Pharmacology Authors: Yuta Suzuki Hiroshi Ishihara Source Type: research

Functional differences between protamine preparations for the transfection of mRNA.
Authors: Jarzebska NT, Lauchli S, Iselin C, French LE, Johansen P, Guenova E, Kündig TM, Pascolo S Abstract Protamine is a natural cationic peptide mixture used as a drug for the neutralization of heparin and in formulations of slow-release insulin. In addition, Protamine can be used for the stabilization and delivery of nucleic acids (antisense, small interfering RNA (siRNA), immunostimulatory nucleic acids, plasmid DNA, or messenger RNA) and is therefore included in several compositions that are in clinical development. Notably, when mixed with RNA, protamine spontaneously generates particles in the size range ...
Source: Drug Delivery - August 18, 2020 Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research

Dry powder form of polymeric nanoparticles for pulmonary drug delivery.
Abstract Delivery to the lungs is an efficient way to deliver drugs directly to the site of action or to the blood circulation. Because of limitations of direct administration of free drugs, particulate drug delivery systems such as DPI formulations based on nanoparticles (NPs) have been of interest for pulmonary drug delivery. The prolonged residence of NPs in the lungs due to ability to escape from the clearance mechanisms such as mucociliary escalator, macrophage uptake (a size of 1-2 µm is ideal for macrophage phagocytosis), and translocation to the systemic circulation is amongst the key advantages of NPs. B...
Source: Current Pharmaceutical Design - January 28, 2016 Category: Drugs & Pharmacology Authors: Shiehzadeh F, Tafaghodi M Tags: Curr Pharm Des Source Type: research

Current advances in self-assembled nanogels for immunotherapy.
Abstract Since nanogels (nanometer-sized gels) were developed two decades ago, they were utilized as carriers of innovative drug delivery systems. In particular, immunological drug delivery via self-assembled nanogels (self-Nanogels) owing to their nanometer size and molecular chaperon-like ability to encapsulate large biomolecules is one of the most well studied and successful applications of nanogels. In the present review, we focus on nanogel applications as immunological drug delivery systems for cancer vaccines, cytokine delivery, nasal vaccines and nucleic acid delivery, including several clinical trials. Ca...
Source: Advanced Drug Delivery Reviews - October 16, 2015 Category: Drugs & Pharmacology Authors: Tahara Y, Akiyoshi K Tags: Adv Drug Deliv Rev Source Type: research

Protamine-oligonucleotide-nanoparticles: Recent advances in drug delivery and drug targeting.
Abstract Application of oligonucleotides as active compounds has become a crucial field of pharmaceutical research in recent years. In order to improve inadequate transfection rate and avoiding rapid enzymatic degradation of antisense oligonucleotides (AS-ODNs) a novel nanoparticulate delivery system was reported by our group at the beginning of 2000. AS-ODNs are condensed by the polycationic peptide protamine into solid particles in the size range of 100-200nm. Nanoparticle formation is driven by a self-assembling process based on electrostatic interactions between the oppositely charged biomolecules. This new de...
Source: European Journal of Pharmaceutical Sciences - April 17, 2015 Category: Drugs & Pharmacology Authors: Scheicher B, Schachner-Nedherer AL, Zimmer A Tags: Eur J Pharm Sci Source Type: research

Development of anti-E6 pegylated lipoplexes for mucosal application in the context of cervical preneoplastic lesions
In conclusion, pegylated anti-E6 lipoplexes have demonstrated their efficiency to cross the cellular membrane and to release siRNA into the cytoplasm confirmed by final p53 protein production. Graphical abstract
Source: International Journal of Pharmaceutics - February 27, 2015 Category: Drugs & Pharmacology Source Type: research

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