Pickering nano-emulsion as a nanocarrier for pH-triggered drug release.

This study investigates the formulation of surfactant-free Pickering nano-emulsions able to release a drug at specific pH, in order to enhance its oral bioavailability. The stabilizing nanoparticles composed of magnesium hydroxide, were obtained by nano-precipitation method. The oil-in-water Pickering nano-emulsions stabilized with Mg(OH)2 nanoparticles, and encapsulating a model of hydrophobic drug (ibuprofen) were formulated following a high-energy process, using a sonication probe. The experimental approach explored the impact of all formulation parameters, composition and size of Mg(OH)2 nanoparticles, on the physico-chemical properties of the Pickering nano-emulsions. The system was characterized by DLS and transmission electron microscopy. In addition, Mg(OH)2 has the advantage of being solubilized in an acid medium leading to the destabilization of the nano-emulsion and the release of the active ingredient orally. The acid release study (pH = 1.2) showed cumulative release as a function of initial nanodroplet loading and saturation concentration. In basic media (pH = 6.8), we found a significant release of ibuprofen from the nano-emulsions that already had saturation in an acid medium. These nano-emulsions can not only protect patients from the side effects of acid medicines through the basic properties of hydroxides but also can contribute to the increase of the bioavailability of these drugs. In addition, once in the stomach pH is increased by hydroxides and promotes the release of active ingredients such as ibuprofen whose solubility is strongly influenced by pH.

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

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.