Time‐Controllable Lipophilic‐Drug Release System Designed by Loading Lipid Nanoparticles into Polysaccharide Hydrogels

Abstract

A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-linked carboxymethylcellulose (CMC) is developed to achieve localized and sustained release of lipophilic drugs. The analysis of LNP stability as well as the hydrogel swelling and mechanical properties confirm the successful incorporation of particles up to a concentration of 50% w/w . The initial LNP release rate can be prolonged by increasing the particle diameter from 50 to 120 nm, while the amount of long-term release can be adjusted by tailoring the particle surface charge or the cross-linking density of the polymer. After 30 d, 58% of 50 nm diameter negatively charged LNPs escape from the matrix while only 17% of positively charged nanoparticles are released from materials with intermediate cross-linking density. A mathematical diffusion model based on Fick's second law is efficient to predict the diffusion of the particles from the hydrogels.

Characterization of Collagen/Lipid Nanoparticle–Curcumin Cryostructurates for Wound Healing Applications

“…It thus appears that, in the time lapse from day 14 to 25, dyes were released partly in the form of encapsulated particles and partly as free molecules (Figure S8, Supporting Information). Similar diffusion patterns have been reported for other lipid nanoparticle/hydrogels (in particular, polysaccharide‐based) by us and others …”

“…The first “burst release” phase could be accounted for by the fast diffusion of LNP directly contacting the water phase, whereas deeper particles would take longer to escape . Apparently, diffusion is more influenced by charge and hydrogel pore size than by particle size . Indeed, as observed here, the diffusion kinetics of F50 was only a bit faster than that of F120 nanoparticles (Figure A).…”

“…Lipid nanoparticle diffusion from hydrogels is a diffusion‐driven process . The first “burst release” phase could be accounted for by the fast diffusion of LNP directly contacting the water phase, whereas deeper particles would take longer to escape . Apparently, diffusion is more influenced by charge and hydrogel pore size than by particle size .…”

Lipid Nanoparticles and Their Hydrogel Composites for Drug Delivery: A Review

“…If it is associated with cross-linkers that induce thermo-gelation [34], the mixing step will be carried out at 4 °C. In the case of photo-activated cross-linking reactions [35], LNP dispersion, modified polysaccharides and associated polymers will be homogeneously dispersed in aqueous solution prior to exposition to UV light. Polysaccharides constitute the third-most used polymer family in LNP-hydrogel composite engineering (Figure 4).…”

“…A second way to control the release of the drug loaded in LNP-hydrogel systems is to play with the density of the hydrogel network. A hybrid hydrogel was developed by Racine and collaborators [35], thanks to a UV photo-activated thiol-ene cross-linking reaction. Adding a second polymer in the hydrogel network makes easier to precisely modulate the density of cross-links.…”