Layer by layer self-assembly for coating a nanosuspension to modify drug release and stability for oral delivery

Layer-by-layer (LbL) modification is an effective way to tune the properties of particles. However, the traditional LbL process involves repeated washing steps which are not compatible with nanoparticles with a partial solubility. In this work, we demonstrate the use of a titration method for producing LbL coatings onto a nanosuspension of curcumin (a compound with a limited aqueous solubility). The aim of the work was to show how LbL can be used to enhance the release behaviour and stability of the curcumin in a nanosuspension form. Coated nanosuspension samples were produced using biocompatible and biodegradable polyelectrolytes, poly-L-arginine, and sodium alginate and was sizes approximately 500 nm. A stimuli-responsive nanosuspension was prepared by coating the nanosuspension with 5 layers of poly-L-arginine and alginate and Eudragit L100 as an outmost layer. The in vitro release of these nanosuspensions revealed that the use of a pH-responsive layer (Eudragit L100) as an outermost shell resulted in delay the release of curcumin (5%) in acidic pH and facilities its release in neutral pH (11%) over 72 h. Additionally, the bioaccessibility study showed that increasing the number of layers resulted in increasing the stability curcumin in nanosuspension when exposed to conditions that mimic the gastrointestinal tract from 20% for uncoated nanosuspension to 40% and 90% for 4-layered coated nanosuspension and stimuli-responsive (6-layered) coated nanosuspension, respectively. The cytotoxicity of LbL-coating of nanosuspension revealed a reduction in the toxicity of curcumin. This work shows how a titrated LbL modification approach could be used to tailor the stability and the release behaviour of nanosuspensions for oral drug delivery applications.