Amine-Modified Poly(Vinyl Alcohol)s as Non-viral Vectors for siRNA Delivery: Effects of the Degree of Amine Substitution on Physicochemical Properties and Knockdown Efficiency

Abstract

DEAPA-PVA polymers were shown to mediate efficient gene silencing and offer a promising platform for further structural modifications.

Controlled Release of Anti-inflammatory siRNA from Biodegradable Polymeric Microparticles Intended for Intra-articular Delivery to the Temporomandibular Joint

“…To date, accurate measurement of siRNA content in siRNA-PEI polyplexes has been a major challenge in the field because siRNA is much smaller than plasmid DNA; thus, PEI entirely blocks binding of fluorescent siRNA-binding dyes (PicoGreen, ethidium bromide, etc.) (8,24). Several studies have reported the use of fluorescent siRNA-binding dyes to quantify siRNA content in siRNA-PEI polyplexes (16,25), without specifying whether siRNA was dissociated from PEI.…”

“…While some publications have reported effective gene silencing by siRNA-PEI polyplexes with 6:1 or 8:1 N:P ratio, others have reported that higher ratios were required (11,13,16,21,24). A recent study of PLA MPs encapsulating polyplexes consisting of murine anti-TNF-α siRNA and 25 kDa branched PEI (16) demonstrated that polyplexes with very low N:P ratio (i.e., 4:1) were not entrapped in PLA MPs fabricated via a technique similar to that used to generate our PLGA MPs.…”

“…The absence of free-PEI in the release samples suggests that the cationic PEI was complexed with PLGA MP derivatives, including small MPs and degradation products, which contain anionic carboxyl groups at physiologic pH (11). This sequestration of PEI is beneficial, since cytotoxicity is a major limitation of PEI as a siRNA transfection vehicle (7,24,29,30). Complexation of excess PEI with anionic PLGA MP derivatives will reduce its interaction with negatively charged cell membranes and thus limit its potential in vivo cytotoxicity (29).…”

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

“…The toxicity of pDMAEMA-pHEMA diblock copolymers was tested using L929 murine fibroblasts in MTT-assays as previously described, using 2mg/mL MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide)-stock solution [38]. As pure polymers are considered to be more toxic than the polyplexes [12,35], the harsher conditions were tested by applying the pure polymer dilutions in a concentration range from 0.5 mg/mL to 0.00029 mg/mL to 96-well plates with 8,000 cells per well, seeded 24 h prior to the experiment.…”

Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro

“…It also has been shown by Wittmar and Nguyen that aminated PVA can cause cytotoxicity in L929 mouse fibroblasts and SKOV-luc human ovary cancer cells. 41,42 The potential for AuNPs to cause a (pro-)inflammatory cellular response was addressed by measuring cytokine secretion. TNF-α and IL-1β have been investigated, since they are involved in lung diseases by the activation of different (pro-)inflammation pathways and the inflammasome activation pathway.…”