Amphiphilic Nanoparticle-in-Nanoparticle Drug Delivery Systems Exhibiting Cross-Linked Inorganic Rate-Controlling Domains

Julia Talal, Inbal Abutbul-Ionita, Inbar Schlachet, Dganit Danino, Alejandro Sosnik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Aiming to explore the potential of sol-gel chemistry to physically stabilize polymeric micelles and confer sustained release features, this work reports for the first time on the production of hybrid organic-inorganic multimicellar nanomaterials that, as opposed to the state-of-the-art materials, display cross-linked poly(siloxane) rate-controlling domains. To achieve this goal, poly(ethylene oxide)-b-poly(propylene oxide) amphiphiles with different architectures (linear and branched) and hydrophilic-lipophilic balances were primarily modified with alkoxysilane moieties through the reaction of the terminal hydroxyl groups of the copolymer and 3-(triethoxysilyl)propyl isocyanate. Then, ethoxysilane-modified polymeric micelles were prepared in water where hydrolysis resulted in a silanol-decorated surface that was cured by spray-drying. Because of the singular spraying mechanism of the Nano Spray-Dryer B-90 used in this work, which is based on a vibrating mesh spray with holes in the 4-7 μm size range that produce ultrafine droplets, a novel kind of hybrid amphiphilic nanoparticle-in-nanoparticle system with high physical stability was developed. Comprehensive microscopy studies demonstrated the multimicellar nature of these novel nanomaterials. Moreover, they hosted large payloads of the hydrophobic model drug tipranavir in the hydrophobic domains and sustained the release with a more controlled zero-order fashion compared to that of the pristine non-cross-linked counterparts that followed the classical biphasic release with an initial burst effect and a subsequent more moderate rate.

Original languageEnglish
Pages (from-to)873-885
Number of pages13
JournalChemistry of Materials
Issue number2
StatePublished - 24 Jan 2017
Externally publishedYes


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