Sonication-Assisted Layer-by-Layer Assembly for Low Solubility Drug Nanoformulation

Sonication-assisted layer-by-layer (LbL) self-assembly is a nanoencapsulation technique based on the alternate adsorption of oppositely charged polyelectrolytes, enabling the encapsulation of low solubility drugs. In this work, a top-down LbL technique was performed using a washless approach and ibuprofen (IBF) as a model class II drug. For each saturated layer deposition, polyelectrolyte concentration was determined by titration curves. The first layer was constituted by cationic poly(allylamine hydrochloride) (PAH), given the IBF negative surface charge, followed by anionic polystyrenesulfonate (PSS). This polyelectrolyte sequence was made up with 2.5, 5.5, and 7.5 bilayer nanoshells. IBF nanoparticles (NPs) coated with 7.5 bilayers of PAH/PSS showed 127.5 +/- 38.0 nm of particle size, a PDI of 0.24, and a high zeta potential (+32.7 +/- 0.6 mV), allowing for a stable aqueous nanocolloid of the drug. IBF entrapment efficiency of 72.1 +/- 5.8% was determined by HPLC quantification. In vitro MTT assay showed that LbL NPs were biocompatible. According to the number of coating layers, a controlled release of IBF from LbL NPs was achieved under simulated intestinal conditions (from 5 h up to 7 days). PAH/PSS-LbL NPs constitute a potential delivery system to improve biopharmaceutical parameters of water low solubility drugs.