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RESEARCH PRODUCT
High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions
S. NummelinJari KoivistoMarkus SelinJarmo RopponenLeena PeltonenLuis M. BimboLuis M. BimboJill DeleuJill DeleuJouni HirvonenManu LahtinenTapani ViitalaMauri A. Kostiainensubject
Recrystallization (geology)huumeetPolymers and Plastics116 Chemical sciences02 engineering and technology01 natural sciencesdrugsContact angleMaterials ChemistryHUMAN LECTINSSurface plasmon resonanceta116chemistry.chemical_classificationChemistryBIOLOGICAL-MEMBRANES021001 nanoscience & nanotechnologyPROGRAMMABLE GLYCAN LIGANDSINDOMETHACIN317 PharmacyCLICK CHEMISTRYfarmaseuttinen kemia0210 nano-technologyHydrophobic and Hydrophilic InteractionsDendrimersSURFACEBioengineeringPoloxamer010402 general chemistryRSPOORLY SOLUBLE DRUGBiomaterialsHydrophobic effectSurface-Active AgentsSuspensionslääkeyhdisteetDendrimerAmphiphileGLYCODENDRIMERSOMESta216ta215AlkylMODULAR SYNTHESISWaterPoloxamerCombinatorial chemistry0104 chemical scienceslääkkeet1182 Biochemistry cell and molecular biologypharmaceutical nanosuspensionsCOMPLEX ARCHITECTURESdescription
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. Peer reviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-10-08 | Biomacromolecules |