Amphiphilic Dendritic Hydrogels with Carbosilane Nanodomains: Preparation and Characterization as Drug Delivery Systems

Carbosilane dendrimers are hyperbranched lip-ophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo. The first family of cleavable carbosilane dendrimers was designed for this purpose, overcoming one of the main drawbacks of these type of dendrimers. Biodegradable dendritic low-swelling hydrogels with aromatic nanodomains were easily prepared using the highly efficient click thiol-ene chemistry. Our studies through electron-paramagnetic resonance, molecular dynamics simulations, and experimental assays confirmed the impact of the carbosilane dendritic nanodomains in both the encapsulation and the release pattern of model drugs such as ibuprofen and curcumin. Curcumin-loaded hydrogels were further tested in in vitro assays against advanced prostate cancer cells. The dendritic hydrogels not only enabled drugs encapsulation; as proof of concept, ibuprofen was efficiently attached via fluoride-promoted esterification and was enzymatically cleaved, achieving a controlled release over time.