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

Abstract

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.

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

“…If brought into clinical practice, long-acting ART regimens would substantively improve drug adherence, reduce secondary toxicities and prevent new infections. These could ultimately facilitate the realization of an AIDS-free world 1 - 8 . In efforts to complete this task, we improved the hydrophobicity of existing antiretroviral drugs (ARVs), leading to the formation of cell- and tissue-penetrant nanocrystals protected inside biodegradable polymers.…”

Hybrid Titanium Oxide/Polymer Amphiphilic Nanomaterials with Controlled Size for Drug Encapsulation and Delivery

“…The process consists of i) the hydrolysis of a metal (M) alkoxide in aqueous medium to form MOH bonds and ii) their condensation under water‐deprived conditions to render an M–O–M network. In previous works, we used Si‐based sol–gel chemistry to synthesize in situ crosslinking thermoresponsive gels and amphiphilic multimicellar nanodrug delivery systems …”

Tailoring liquid crystals as vehicles for encapsulation and enzyme-triggered release

“…This has been addressed by complexation of the drug molecule to the micellar core, which can be disrupted under certain conditions. 41 We hypothesized that the presence of a defined hydrophobic core of LC droplets might facilitate the sustained release of hydrophobic drug candidates. Nile Red (NR) is widely used as a model hydrophobic probe in the design of nanoscaffolds for drug delivery applications.…”