Multilayer Coating of Gold Nanoparticles with Drug−Polymer Coadsorbates

Abstract

The aim of our present study was the development of a drug multilayer-based carrier system for delivery of water-insoluble drugs. As drug, we applied the anticancer drug 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin, mTHPP, which is a model photosensitizer for photodynamic therapy. Gold nanoparticles (AuNP) with a diameter of 14.5 ± 0.9 nm were prepared and used as template for the layer-by-layer approach. The drug and the negatively charged polyelectrolyte (PE) poly(styrene sulfonate) sodium salt (PSS) were complexed with a new developed method using freeze-drying. The complexation efficiency was determined to be ∼11-12 monomers PSS per mTHPP molecule by CHNS analysis and UV/vis measurement. Molecular docking simulations revealed π-π interactions and H-bonding to be the responsible mechanisms. A drug multilayer system based on the layer-by-layer (LbL) technique utilized the water-soluble complex as anionic layer material and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified AuNP were characterized by different physicochemical techniques such as UV/vis, ζ-potential, ICP-OES, and TEM. To the best of our knowledge, we could demonstrate for the first time the adsorption of three drug layers to a nanoparticulate system. Furthermore, the adaptation of the LbL-technique resulted in drastically increased drug deposition efficiency (factor of 100). Furthermore, we developed a new and comfortable way to solubilize water-insoluble drugs in water.

Setup for investigating gold nanoparticle penetration through reconstructed skin and comparison to published human skin data

“…This data would then allow comparison of results obtained using SE with previous experiments on full-thickness HS we conducted with the same particles in our laboratory, 7,8 thus eliminating inter-laboratory variations. AuNP were chosen as a good model for studying skin penetration of nanoparticles due to their unique optical properties 23,26,29,30 in addition to their potential as drug carriers.…”

Lipid-coated gold nanocomposites for enhanced cancer therapy

“…29,30 Colloidal nanoparticle-based drug delivery has been considered as a potential tool with remarkable abilities in cancer imaging and therapeutics. [31][32][33][34][35][36] Encapsulating nanoparticles in lipid vehicles is an alternative approach that has been used in recent years to achieve controlled drug delivery and implement combined therapy. Therefore, the co-delivery of drug and nanoparticle is becoming a standard strategy in cancer therapy, since it substantially reduces the necessary DTX dose and improves …”

Could Chemical Enhancement of Gold Nanoparticle Penetration Be Extrapolated from Established Approaches for Drug Permeation?

“…Ionically-stabilized, polar AuNP (AuNP1) were prepared according to the Turkevich method [15,27]. Briefly, 70 ml hydrogen tetrachloroaurate solution (HAuCl 4 · 3H 2 O, Sigma-Aldrich Chemie GmbH, Steinheim, Germany) containing about 100 µg/ml gold was reduced by trisodium citrate dihydrate (Na 3 C 6 H 5 O 7 · 2H 2 O, Sigma-Aldrich) containing 5-fold the molar concentration of gold salt at 100°C.…”

“…Enhancement of skin penetration of AuNP holds promise in dermatology due to its high clinical significance. AuNP have recently emerged as a delivery system of various payloads [10,11,12] ranging from drug molecules [13,14,15] to large biomolecules [16,17,18,19]. In addition, their physical properties could be exploited.…”