Predicting the release profile of small molecules from within the ordered nanostructured lipidic bicontinuous cubic phase using translational diffusion coefficients determined by PFG-NMR

Abstract

The ordered nanostructured lipidic bicontinuous cubic phase has demonstrated potential as a drug release material, due to its ability to encapsulate a wide variety of compounds, which may undergo sustained, diffusion controlled release over time. Control of drug release has been shown to depend on the nanostructural parameters of the lipid mesophase. Herein, the diffusion and release of two amino acids, encapsulated within a range of different lipidic cubic mesophases are investigated. Pulsed-field gradient NMR was used to determine the diffusion coefficient of the encapsulated amino acid, which was found to be correlated with the nanoscale diameter of the water channels within the cubic mesophase. This information was used to predict the release profiles of encapsulated compounds from within the cubic mesophase, which was verified by directly measuring the release of each amino acid in vitro. Predicted release profiles tracked reasonably close to the measured release profiles, indicating that NMR determined diffusion measurements can be used to predict release profiles.

Evidence of superdiffusive nanoscale motion in anionic polymeric hydrogels: Analysis of PGSE- NMR data and comparison with drug release properties

“…to estimate solute diffusion coefficients from experimental release data, or to infer the solute transport mechanism. [32,35] In some cases, [33,36,37] the diffusion coefficients obtained by this approach have been successfully compared with experimental ones. Nonetheless, due to the time scale of release experiments (typically minutes/hours), such estimates alone cannot be expected to clarify the mechanisms of solute transport on the molecular scale.…”

Impact of Molecular Partitioning and Partial Equilibration on the Estimation of Diffusion Coefficients from Release Experiments

“…[43], a layer of bound water of thickness ∼ 0.6 nm was assumed). This value is larger than the best estimation offered by the case Δ = 0.5 h (see table 1), which indicates that caffeine is spending a significant amount of time within the lipid bilayer, where the diffusion coefficient is expected to be ∼ 10 2C cm 2 /s or lower 23 , thus resulting into a smaller overall value of the effective diffusion coefficient ' .…”

“…Being a mixture of lipids and water, the resulting mesophases can entrap molecules with different amphiphilicity. These characteristics have made them suitable candidates for drug delivery studies, where the release kinetics can be controlled by tuning the details of the system, particularly the geometrical details of the mesophase and the interactions of the drug with the LLC matrix 2,6,15,[17][18][19][20][21][22][23][24][25] . Among lipid mesophases, inverse bicontinuous cubic phases (IBCPs) are especially suitable for drug-delivery purposes, as fast release is achieved thanks to their three-dimensional periodic porous network 25 .…”

Self-Assembled Lipid Cubic Phase and Cubosomes for the Delivery of Aspirin as a Model Drug

“…Apparent Fickian diffusion is known to contribute in sustaining the release of small molecules from bulk cubic phases [30][31][35][36][37][38][39] . This can be easily attributed to the highly tortuous porous morphology of cubic phases.…”

“…A few recent reports demonstrate that the release rates from lipid systems can be controlled by fine-tuning nanostructural type and dimensions of the self-assembled phases [30][31][32][60][61][62] . For instance, if the nanostructure is hexagonal phase, the release can be more controlled in…”