Chitosan/tripolyphosphate nanoparticles are promising drug delivery systems, which show excellent capacity for protein entrapment and improvement of mucosal peptide absorption. We have recently developed a new drug delivery system consisting of assemblies formed between preformed chitosan nanoparticles and phospholipids (dipalmitoylphosphatidylcholine and dimiristoylphosphatidyl-glycerol) which are endogenous to the lung. These assemblies are prepared by lipid film hydration with a nanoparticles suspension. The aim of this work was to elucidate the architecture of these structures using sensitive surface analysis techniques such as X-ray photoelectron spectroscopy and static time-of-flight secondary ion mass spectrometry, as well as to determine their physicochemical characteristics. The combination of zeta potential measurements with the results obtained by X-ray photoelectron spectroscopy and static time-of-flight secondary ion mass spectrometry, demonstrated that a complete lipid coating of the nanoparticles can be achieved using a lipid film formed by both dipalmitoylphosphatidylcholine and dimiristoylphosphatidylglycerol, this way conferring to the lipid film a strong negative charge, which favors the interaction with the positively charged nanoparticles. Therefore, the major role of electrostatic interactions as driving forces to control the organisation of the lipid/nanoparticles assemblies was clearly evident. The implications of these findings for the structural organisation of the assemblies, for their in vitro behaviour, as well as for their mechanism of formation are discussed.
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