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Development of lipid nanoparticles for delivery of siRNA to neural cells
Lipid nanoparticles (LNPs) are a clinically approved platform to deliver siRNA to the liver. We are optimizing this platform to deliver siRNA for the treatment of pain. siRNA against TRPV1 (siTRPV1) was chosen as a proof of concept. siTRPV1-LNPs were formulated using C12-200, an ionizable cationic lipid and helper lipids. Their particle size and surface charge was characterized using dynamic light scattering and siRNA encapsulation efficiency was determined using a Ribogreen assay. A panel of breast cancer cell lines (MCF-7, MDA-MB-231 and BT-549) that express TRPV1 were selected for in vitro screening of LNPs to determine...
Source: The Journal of Pain - May 1, 2021 Category: Materials Science Authors: Purva Khare, Kandarp Dave, Jane Hartung, Michael Gold, Devika Manickam Source Type: research

Development of an activated microglia cell line model for screening lipid nanoparticle formulations of BDNF siRNA for neuropathic pain therapy
Purpose Brain-derived neurotrophic factor (BDNF) released from activated spinal microglia via the ATP-P2  × 4R-BDNF signaling pathway plays a central role in initiating pain hypersensitivity in neuropathic pain. Therefore, knockdown of BDNF expression in microglia using molecules like siRNA can be a promising strategy for neuropathic pain therapy. Our lab is developing lipidoid nanoparticles (LNP) for the delivery of BDNF siRNA (siBDNF) for treating neuropathic pain. We characterized the Spontaneously Immortalized Microglia-A9 (SIM-A9) cell line and confirmed the expression of Iba1, P2 × 4R, and BDNF under restin...
Source: The Journal of Pain - May 1, 2021 Category: Materials Science Authors: Kandarp Dave, Lalah Ali, Devika S Manickam Source Type: research

Valproate Prevents Dysregulation of Spinal Glutamate and Reduces the Development of Hypersensitivity in Rats After Peripheral Nerve Injury
This study demonstrates that valproate prevents the downregulation of glutamate transporters in the spinal cord, which contributes in part to the development of chronic pain after nerve injury. Given clinical availability and established safety profiles, perioperative use of valproate should be tested to prevent chronic pain after surgery.
Source: The Journal of Pain - September 9, 2013 Category: Materials Science Authors: Masaru Yoshizumi, James C. Eisenach, Ken-ichiro Hayashida Tags: Original Reports Source Type: research