Side‐effects of a systemic injection of linear polyethylenimine–DNA complexes

Abstract

This study demonstrates that L-PEI/DNA activates the lung endothelium and forms small aggregates, a side-effect linked to the transfection efficiency.

Induction of gp120-specific protective immune responses by genetic vaccination with linear polyethylenimine–plasmid complex

“…Among the strategies being evaluated to increase the efficiency of DNA vaccination is the use of non-viral vectors to deliver the DNA. One such vector, PEI 22, has been previously described to efficiently deliver reporter genes in vivo, with particularly high expression in the lungs and lower expression in other organs like the spleen, kidney and liver [34]. Here, we show that PEI22-DNA complex shortly-6 h-after intravenous injection, induces high levels of IL-12 and IFN-␥ in the serum.…”

“…1B). Surprisingly, low levels of IL-12 and IFN-␥ were detected in the organ that showed the highest transgene expression 6 h after PEI-pluciferase administration, the lung [34].…”

“…administration of PEI-DNA complexes has been described as lung embolism and liver injury [34]. In order to assess the toxicity of our PEI-pgp120 complexes, we looked at the morbidity and mortality of injected mice, and measured biochemical parameters that indicate liver injury.…”

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

“…Severe toxicity to healthy organs consistently occurred following systemic injection of cationic vectors 9. After five intravenous injections at a PTX dose of 10 mg kg −1 or at 10 mg kg −1 of CLG or 5 mg kg −1 PEI into BALB/c mice, the main organs were collected and then subjected to H&E analysis at day 16.…”

“…Nevertheless, the highly positive charge stems from the high density of amines on these vectors, which generates strong toxic effects; even at very low doses, the toxicity is still intense, hindering their further clinical application. Severe side effects, such as liver necrosis, shock response, and acute pulmonary embolism, have been observed following the intravenous injection of 1.5 × 10 −6 m PEI (22 kDa) into mice with a body weight of 20 g 9. Second, after injection, these conventional cationic vectors bind to serum protein and thus are rapidly removed from the blood, with a circulation time less than 10 min,10 thus preventing localization to the desired tissues.…”