Architectural layer-by-layer assembly of drug nanocapsules with PEGylated polyelectrolytes

Abstract

150–200 nm diameter capsules containing 60–70 wt % of poorly soluble drugs, paclitaxel and camptothecin, were produced by layer-by-layer (LbL) assembly on drug nanocores in a solution containing uncharged stabilizers. Optimization of capsule shell architecture and thickness allowed for concentrated (3–5 mg/mL) colloids that are stable in isotonic salt buffers. Nanoparticle aggregation during the washless LbL-assembly was prevented by using low molecular weight block-copolymers of poly(amino acids) (poly-L-lysine and poly-L-glutamic acid) with polyethylene glycol (PEG) in combination with heparin and bovine serum albumin at every bilayer building step. Minimal amounts of the polyelectrolytes were used to recharge the surface of nanoparticles in this non-washing LbL process. Such PEGylated shells resulted in drug nanocapsules with high colloidal stability in PBS buffer and increased protein adhesion resistance. The washless LbL polyelectrolyte nanocapsule assembly process, colloidal stability and nanoparticle morphology were monitored by dynamic light scattering and electrophoretic mobility measurements, UV-vis spectroscopy, TEM, SEM and laser confocal microscopy imaging.

Polyelectrolyte-coated nanocapsules containing undecylenic acid: Synthesis, biocompatibility and neuroprotective properties

“…As undecylenic acid is practically not soluble in water (the logP (Poctanol/water partition coefficient) is higher than 3,86 (Material Safety Data Sheet, Sigma Aldrich, W324701) we assumed 100% efficiency of encapsulation. Consequently, without solubility enhancer (such as Polysorbate 80) added to the release media prior to the experiments [15] the released drug concentrations were very difficult to monitor. However, such conditions do not fulfill the in vivo criteria, so that on the basis of such in vitro release experiments the expected in vivo biological effects of the produced nanocapsules cannot be accurately foreseen.…”

“…emulsion) core surrounded by a polymeric functionalized shell [9]. There is a number of research on encapsulation of nano-or microemulsion droplets by the sequential adsorption of (bio)polyelectrolytes to form nanocarierrs as drug delivery vehicles for hydrophobic drugs [10][11][12][13][14][15][16]. Nanocapsules exhibit similarity in their size and morphology to the natural occurring carriers such as serum lipoproteins [17].…”

Polysaccharide Encrusted Multilayered Nano-Colloidal System of Andrographolide for Improved Hepatoprotection

“…The MLNE was prepared in two steps with method described elsewhere with a slight modification (9,21). Firstly, AP (250 mg) was dissolved in sufficient amount of ethanol (oil phase) and then mixed with tween 80 in proportion 1:2 of oil phase.…”

Layer-by-layer nanoencapsulation of camptothecin with improved activity

“…Several formulations based on nanoparticle technology (Chen et al, 2011; Keck et al, 2008; Lee et al, 2008; Kahlweit, 2008; Parikh and Selvaraj, 2008; Müller et al, 2008) have been developed for oral or intramuscular injections, but only few of them are intended for intravenous injection as albumin-based nanoparticles containing paclitaxel (Abraxane ® ) (Kim et al, 2008; Cho et al, 2004; Wei et al, 2010). Another strategy, namely, injectable nanocapsules based on crystalline core of poorly soluble anticancer drugs stabilized with a thin shell of biopolyelectrolytes assembled via layer-by-layer (LbL) assembly technique, was recently reported (Shutava et al, 2012). …”

“…LbL assembly provides an opportunity to form a nano-thick coating in a controllable manner on the surfaces of variable curvature and size from interacting oppositely charges polyelectrolyte components (Shutava et al, 2012; Lvov, 2000; Sukhorukov, 2002; De Geest et al, 2009; Schneider and Decher, 2004; Chodanowski and Stoll, 2001; Li et al, 1994; Kong et al, 1998; Vertegel et al, 2004; Mu et al, 2012; Lu and Liu, 2012). Anchored to the core surface, the thin shell of hydrophilic polyelectrolytes allow exchange of excipients used on the core preparation.…”