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PLA‐PEG Nanospheres: New Carriers For Transmucosal Delivery Of Proteins And Plasmid DNA
Published 2002 · Materials Science
There is little doubt that advances in polymer synthesis and in the design of delivery systems will have a profound impact on future therapeutics and immunization practices based on complex molecules such as proteins and plasmids. Our approach in this area has been the design of nanoparticles made of poly(lactic acid)-poly(ethyleneglycol) (PLA-PEG), for mucosal delivery of proteins and plasmid DNA. The technologies for the formation of these nanoparticles, were conveniently adapted in order to encapsulate proteins efficiently (i.e., tetanus toxoid) and DNA (i.e., pCMV-βGal) into a PLA core coated by PEG. These techniques include the w/o/w emulsion–solvent evaporation technique and the w/o emulsion–solvent diffusion technique, both providing high protein/DNA loadings. Results showed that the presence of a PEG coating around the nanoparticles significantly enhanced their stability in the gastrointestinal fluids, as well as in contact with mucus enzymes. This coating was also found to be responsible for the enhanced transport of 125I-radiolabelled tetanus toxoid and its delivery to the blood circulation and the lymph nodes, following nasal administration to rats. Additionally, fluorescent microscopy studies aimed at examining the interaction and transport of the nanoparticles through the nasal mucosa demonstrated that these nanoparticles can, indeed, cross the nasal epithelium. Finally, the efficacy of these PEG-coated nanoparticles as nasal vaccine delivery vehicles was shown in vivo. More specifically, the tetanus toxoid-loaded nanoparticles were able to elicit enhanced and long-lasting immunogenic responses following nasal administration. On the other hand, a single dose of encapsulated DNA administered intranasally led to a significant systemic antibody response to the encoded protein, confirming that plasmid DNA can be encapsulated in PLA-PEG nanoparticles with significant retention of biological function. To summarize, the data reported in the present paper provide evidence of the potential of PLA-PEG nanoparticles as carriers for the transport of proteins and DNA across mucosal surfaces. Copyright © 2003 John Wiley & Sons, Ltd.