Stimuli‐Responsive Lipidic Cubic Phase: Triggered Release and Sequestration of Guest Molecules

Abstract

New stimuli-responsive nanomaterials, made up of host-guest lipidic cubic phases (LCPs) are presented. These biocompatible, stable, transparent and water-insoluble LCPs are composed of monoolein (MO) as a neutral host, and small amounts of one of three judiciously designed and synthesized designer lipids as guest that preserve the structure and stability of LCPs, but render them specific functionalities. Efficient pH- and light-induced binding, release and sequestration of hydrophilic dyes are demonstrated. Significantly, these processes can be performed sequentially, thereby achieving both temporal and dosage control, opening up the possibility of using such LCPs as effective carriers to be used in drug delivery applications. Specifically, because of the inherent optical transparency and molecular isotropy of LCPs they can be envisaged as light-induced drug carriers in ophthalmology. The results presented here demonstrate the potential of molecular design in creating new functional materials with predicted operating mode.

Design of Light-Triggered Lyotropic Liquid Crystal Mesophases and Their Application as Molecular Switches in “On Demand” Release

“…1 These results are in good agreement with our previously published work. 7 Negrini et al have demonstrated that drug release from a Pn3m cubic phase is ca. 4 times faster than that from a hexagonal phase (H II ).…”

“…Experiments with MG in LCPs composed of MO/1/PBS = 59:1:40 (%, w/w) demonstrate a fast release of the hydrophilic dye in the absence of electrostatic interactions between the lipid head groups and the dye embedded in the aqueous channels, with 45% of the dye released within 8 h. These results are in perfect agreement with the control of release via host−guest electrostatic interactions in cubic phases reported recently. 7,34 Upon the addition of the anionic lipid OA at levels of 1 and 5% (w/w) into the LCPs at pH 7.4, the negatively charged carboxylate headgroup binds the dye more efficiently than the neutral glycerol headgroup of MO ( Figure 2). Increasing the amount of OA from 1 to 5% does not alter the release profile, because already at a level of 1%, the binder (OA) is in large excess with respect to the positively charged dye (n OA /n MG = 364:1).…”

“…6 Finally, another regime is obtained with mesophase systems that contain o-nitrobenzyl-derivatized lipids. 7 These undergo irreversible photochemical cleavage reactions that can switch the charge of their headgroups, thereby affecting binding and release of the drug molecules.…”

“…19 Lipidic mesophases (LMPs) constitute alternative delivery systems that can be triggered by external stimuli. 7,20 One of the most commonly used lipids for the formation of LMPs is monoolein (MO), which exhibits one-, two-, and three-dimensional self-assembled mesophases in the presence of water, corresponding to the hexagonal (H), lamellar (L), and lipidic cubic phases (LCPs). 21,22 The hexagonal phase consists of an ensemble of micellar cylinders packed into a hexagonal lattice.…”

Effects of High Pressure on Internally Self-Assembled Lipid Nanoparticles: A Synchrotron Small-Angle X-ray Scattering (SAXS) Study

“…Moreover, these investigations are beneficial for the potential use of these nano-objects in a range of biotechnological applications, where the stability of the original phase and inter-transitions could play important roles, e.g. for drug delivery applications [26][27][28] .…”