Functionalizing Nanoemulsions with Carboxylates: Impact on the Biodistribution and Pharmacokinetics in Mice

Abstract

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.

Controlling nanoemulsion surface chemistry with poly(2-oxazoline) amphiphiles

“…[31][32][33][34] While these emerging applications showcase the potential versatility of emulsions, liquid droplets remain underdeveloped compared to other so materials. 11,12,35 Currently, a challenge in the preparation of emulsions is decoupling the size and surface charge of the materials. 36,37 Furthermore, chemically robust approaches to append functionality to the surface of emulsions are limited in comparison to conventional nanoparticles.…”

“…36,37 Furthermore, chemically robust approaches to append functionality to the surface of emulsions are limited in comparison to conventional nanoparticles. 12,13,35,38,39 Surfactants play Fig. 1 (A) Surfactants dictate the size, charge, and surface chemistry of emulsions.…”

“…49 This competitive absorption mechanism allows for surface chemistry alteration, 53 but risks desorption of the modied surfactant. 35 Other post-emulsication strategies rely on reversible chemical interactions with the surfactant at the liquid-liquid interface. Reported approaches involve electrostatic deposition, 54-56 designer peptide amphiphiles, 42,57,58 or reactive copolymer surfactants for disulde exchange.…”

Recent Advances in Polyesters for Biomedical Imaging

“…A vast number of publications have investigated the use of polyester contrast agents for the enhancement of X‐ray scanning in both in vitro and in vivo . In 2015, a novel radiopaque 3D printable bone screw based on a poly‐ l ‐lactide composite, which contained 20% IONPs (Fe 3 O 4 ), was reported.…”

“…Vandamme and co‐workers have been exploring different kinds of nontoxic, blood pool X‐ray imaging agents, two of which are polyester based formulations. One of the polyesters was synthesized via encapsulation of iodine into poly(ethylene glycol)‐poly(ε‐caprolactone) nanocapsules, which served as the X‐ray CT contrast agent, avoiding inorganic materials in the formulation .…”