High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions
| Autor: | Sami Nummelin, Jari Koivisto, Markus Selin, Jarmo Ropponen, Leena Peltonen, Luis M. Bimbo, Jill Deleu, Jouni Hirvonen, Manu Lahtinen, Tapani Viitala, Mauri A. Kostiainen |
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| Přispěvatelé: | University of Helsinki, Biohybrid Materials, VTT Technical Research Centre of Finland, University of Jyväskylä, Department of Chemistry and Materials Science, Department of Bioproducts and Biosystems, Aalto-yliopisto, Aalto University, Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Division of Pharmaceutical Biosciences, Pharmaceutical biophysics group, Drug Research Program, Jouni Hirvonen / Principal Investigator, Preclinical Drug Formulation and Analysis group |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Recrystallization (geology)
huumeet Polymers and Plastics 116 Chemical sciences 02 engineering and technology 01 natural sciences drugs Contact angle Materials Chemistry HUMAN LECTINS Surface plasmon resonance ta116 chemistry.chemical_classification Chemistry BIOLOGICAL-MEMBRANES 021001 nanoscience & nanotechnology PROGRAMMABLE GLYCAN LIGANDS INDOMETHACIN 317 Pharmacy CLICK CHEMISTRY farmaseuttinen kemia 0210 nano-technology Hydrophobic and Hydrophilic Interactions Dendrimers SURFACE Bioengineering Poloxamer 010402 general chemistry RS POORLY SOLUBLE DRUG Biomaterials Hydrophobic effect Surface-Active Agents Suspensions lääkeyhdisteet Dendrimer Amphiphile GLYCODENDRIMERSOMES ta216 ta215 Alkyl MODULAR SYNTHESIS Water Combinatorial chemistry 0104 chemical sciences lääkkeet 1182 Biochemistry cell and molecular biology pharmaceutical nanosuspensions COMPLEX ARCHITECTURES |
| Zdroj: | 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 |
| ISSN: | 1526-4602 1525-7797 |
| DOI: | 10.1021/acs.biomac.8b00931 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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