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Journal Article
Research Support, Non-U.S. Gov't
Functionalizing Nanoemulsions with Carboxylates: Impact on the Biodistribution and Pharmacokinetics in Mice.
Macromolecular Bioscience 2017 July
Efficiency of drug administration is related to the inhibition of adverse effects, and can be improved by drug targeting through lipid nanocarriers encapsulation. Targeting technology generally goes along with the nanocarrier functionalization that can be surface modification and/or ligand grafting. The great advantage of nanoemulsions is their loading capability and the possibilities to encapsulate several entities in a single droplet, however, the decoration of the lipid droplets with strongly anchored reactive functions is challenging. This study proposes a reliable and innovative method to functionalize lipid droplets, based on the lipophilic polymer poly(maleic anhydride-alt-1-octadecene), solubilized in the droplet core, and able to hydrolyze at the oil/water interface. Interfacial chemistry and physicochemical properties of nanodroplets are characterized. In vitro studies reveal that the presence of carboxylates at interface has a strong impact on the interactions with cells, as the internalization of functionalized droplets is much higher than control ones. This difference is confirmed with longitudinal computed tomography studies in mice after i.v. administration, strongly impacting the pharmacokinetics and biodistributions. This work establishes the proof-of-concept of a new method for functionalizing lipid droplets and demonstrates that surface modification can have a significant impact on their interaction with cells, pharmacokinetics, and biodistribution.
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