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

Abstract

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.

In Vitro and In Vivo Evaluation of PEGylated Layer‐by‐Layer Polyelectrolyte‐Coated Paclitaxel Nanocrystals

“…However, small or no differences were observed between the formulations, which suggest that most of the PTX was released within the first 24 h. This is consistent with the release profiles obtained in sink conditions (Figure d). Importantly, there was no additional toxicity induced by the presence of the multilayer polyelectrolyte shell, which is in line with what has been reported for other multilayer encapsulated drug nanocores . Moreover, red blood cells (RBCs) exposed to both Abraxane and NC/PSS 70 (PLR/PSS 17 ) 3 ‐PEG (at PTX concentrations similar to those present in the blood after i.v.…”

Layer‐by‐Layer Coating of Solid Drug Cores: A Versatile Method to Improve Stability, Control Release and Tune Surface Properties

“…When the intrinsic charge is insufficient for this, an ionic stabilizer that strongly interacts with the surface of the colloidal particle via nonelectrostatic interactions must be used. Additionally, in order to avoid the formation of separate drug‐free polyelectrolyte complexes during the LbL process, the particles need to be purified from the excess of nonadsorbed polyelectrolyte prior to LbL assembly or alternatively the minimum amount of polyelectrolyte needed to reverse the surface charge must be determined by titration …”

Washless Method Enables Multilayer Coating of an Aggregation‐Prone Nanoparticulate Drug Delivery System with Enhanced Yields, Colloidal Stability, and Scalability

“…The separation is necessary to add the next layer of oppositely charged PE, which otherwise will associate with unbound excess of the previous PE. The high energy step causes the nanoparticles to aggregate, as even when excess PEs are used full coatings cannot be achieved, and colloidal strength is relatively poor . The result is the loss of nanoparticles with each coating step leading to very low yields as the number of layers increases, and decreasing the repeatability of the procedure .…”

“…The high energy step causes the nanoparticles to aggregate, as even when excess PEs are used full coatings cannot be achieved, and colloidal strength is relatively poor. [21,26] The result is the loss of nanoparticles with each coating step leading to very low yields as the number of layers increases, and decreasing the repeatability of the procedure. [27] The method has been used mostly with magnetic core nanoparticles as those can be separated from excess PEs using magnets.…”