High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions

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Selin , M , Nummelin , S , Deleu , J , Ropponen , J , Viitala , T , Lahtinen , M , Koivisto , J , Hirvonen , J , Peltonen , L , Kostiainen , M A & Bimbo , L M 2018 , ' High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions ' , Biomacromolecules , vol. 19 , no. 10 , pp. 3983-3993 . https://doi.org/10.1021/acs.biomac.8b00931

Title: High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions
Author: Selin, Markus; Nummelin, Sami; Deleu, Jill; Ropponen, Jarmo; Viitala, Tapani; Lahtinen, Manu; Koivisto, Jari; Hirvonen, Jouni; Peltonen, Leena; Kostiainen, Mauri A.; Bimbo, Luis M.
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
Date: 2018-10
Language: eng
Number of pages: 11
Belongs to series: Biomacromolecules
ISSN: 1525-7797
URI: http://hdl.handle.net/10138/301155
Abstract: Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydro- philic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.
Subject: PROGRAMMABLE GLYCAN LIGANDS
POORLY SOLUBLE DRUG
COMPLEX ARCHITECTURES
BIOLOGICAL-MEMBRANES
MODULAR SYNTHESIS
CLICK CHEMISTRY
HUMAN LECTINS
GLYCODENDRIMERSOMES
INDOMETHACIN
SURFACE
1182 Biochemistry, cell and molecular biology
116 Chemical sciences
317 Pharmacy
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