Abstract
Nanoparticle-mediated drug delivery has long utilized PEGylation as a mechanism for reducing uptake by the reticuloendothelial system and extending circulation lifetimes. However, studies over the past 2 decades have established that immune responses to PEG can promote clearance on repeat injection and elicit life-threatening anaphylactic reactions in some patients. As a potential alternative to PEGylation, we explored the ability of utilizing lactose, a naturally occurring sugar that is common on the surface of blood cells, as a coating for lipoplexes. Our data indicate that lactose imparts similar effects as PEG in terms of reducing leukocyte uptake, extending circulation half-life, and enhancing delivery to the tumor and other organs. In addition, measurements of blood cytokine levels after repeat injection indicate that reduced levels of inflammatory cytokines (IL-6, IFN-γ, TNFα) are elicited in response to lipoplexes coated with lactose as compared to PEG. These data indicate that a lactose coating on lipoplexes results in slightly improved tumor accumulation as compared to PEGylated formulations while eliciting a reduced innate immune response.
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