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The role of lipid components in lipid nanoparticles for vaccines and gene therapy
Adv Drug Deliv Rev. 2022 Jul 1:114416. doi: 10.1016/j.addr.2022.114416. Online ahead of print.ABSTRACTLipid nanoparticles (LNPs) play a key role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand how this 'key' works, we need to learn about the building blocks that constitute LNPs. In this review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulati...
Source: Advanced Drug Delivery Reviews - July 5, 2022 Category: Drugs & Pharmacology Authors: Camilla Hald Albertsen Jayesh Kulkarni Dominik Witzigmann Marianne Lind Karsten Petersson Jens B Simonsen Source Type: research

Tetrahydroxy stilbene glycoside alleviated inflammatory damage by mitophagy via AMPK related PINK1/Parkin signaling pathway.
In conclusion, these phenomena suggested that TSG prevented LPS/ATP and Aβ-induced inflammation via AMPK/PINK1/Parkin-dependent enhancement of mitophagy. We found the neuroprotective effect of TSG, suggesting it may be beneficial for AD prevention and treatment by suppressing the activation of inflammation. PMID: 32353422 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - April 26, 2020 Category: Drugs & Pharmacology Authors: Gao Y, Li J, Li J, Hu C, Zhang L, Yan J, Li L, Zhang L Tags: Biochem Pharmacol Source Type: research

Lipid-based siRNA Nanodelivery Systems: a Learning Process for Improving Transfer from Concepts to Clinical Applications.
CONCLUSION: Formulation design should be increasingly addressed with industrial criteria; it should be based on quality by design and on the estimation of critical attributes that affect performance, and supported by a range of characterization techniques and appropriate analytical methods. PMID: 30160217 [PubMed - as supplied by publisher]
Source: Current Clinical Pharmacology - August 29, 2018 Category: Drugs & Pharmacology Authors: Perez SE, Carlucci AM Tags: Curr Clin Pharmacol Source Type: research

Nanovehicle-based small interfering RNA (siRNA) delivery for therapeutic purposes: a new molecular approach in the pharmacogenomics.
Abstract RNA interference (RNAi) is a process for regulating the gene expression in which small interfering RNAs (siRNAs) silence target genes. siRNA-based therapy as a new molecular treatment approach, offers therapeutic prospects for many common diseases such as cancer and cardiovascular disorders. Nevertheless, the efficacy of siRNA delivery has, so far, remained a challenging issue. This is due to their easy degradation through the circulation system and the difficulties in the intracellular delivery to specific tissues where they silence the target genes. There have been many efforts to develop suitable, safe...
Source: Current Clinical Pharmacology - July 9, 2018 Category: Drugs & Pharmacology Authors: Akhtari J, Tafazoli A, Mehrad-Majd H, Mahrooz A Tags: Curr Clin Pharmacol Source Type: research

Activation of α7 nicotinic acetylcholine receptors increases intracellular cAMP levels via activation of AC1 in hippocampal neurons.
Abstract The activation of α7 nAChRs has been shown to improve hippocampal-dependent learning and memory. However, the molecular mechanism of α7 nAChRs' action remains elusive. We previously reported that activation of α7 nAChRs induced a prolonged enhancement of glutamatergic synaptic transmission in a PKA-dependent manner. Here, we investigated any connection between the activation of the α7 nAChR and cAMP signaling in hippocampal neurons. To address this question, we employed a FRET-based biosensor to measure the intracellular cAMP levels directly via live cell imaging. We found that application of the α7 ...
Source: Neuropharmacology - April 29, 2015 Category: Drugs & Pharmacology Authors: Cheng Q, Yakel JL Tags: Neuropharmacology Source Type: research