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Nonetheless, it demands for the design of especially tailored formulations. Here, lipid\/poly(lactic\u2010co\u2010glycolic) acid (PLGA) hybrid nanoparticles (hNPs) for the combined delivery of an antigen, ovalbumin (Ova), and an adjuvant, synthetic unmethylated cytosine\u2010phosphate\u2010guanine oligodeoxynucleotide (CpG) motifs, is developed. A panel of Ova\/CpG\u2010loaded lipid@PLGA hNPs with tunable size and surface is attained by exploiting two lipid moieties, 1,2 distearoil\u2010sn\u2010glycero\u20103\u2010phosphoethanolamine\u2010poly(ethylene glycol) (DSPE\u2010PEG) and monophosphoryl lipid A (MPLA), with or without polyethyleneimine (PEI). It is gained insights on the lipid@PLGA hNPs through a combination of techniques to analytically determine the specific moiety on the surface, the spatial distribution of the components and the internal structure of the nanoplatforms. The collected results suggest that PEI plays a role of paramount importance not only in promoting in vitro antigen escape from lysosomes and enhancing antigen cross\u2010presentation, but also in determining the arrangement of the moieties in the final architecture of the hNPs. Though multicomponent PEI\u2010engineered lipid@PLGA hNPs turn out as a viable strategy for delivery of antigens and adjuvant to the respiratory mucosa, tunable nanoparticle features are achievable only through the optimal selection of the components and their relative amounts.<\/jats:p>","DOI":"10.1002\/adhm.202402688","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:09:10Z","timestamp":1726031350000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["PEI\u2010Engineered Lipid@PLGA Hybrid Nanoparticles for Multimodal Delivery of Antigens and Immune Adjuvants to the Respiratory Mucosa"],"prefix":"10.1002","volume":"13","author":[{"given":"Susy","family":"Brusco","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via D. 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