(95a) Silicate Prodrug-Loaded Nanoparticles

Nanoparticles of highly insoluble drugs can be created by flash nanoprecipitation, FNP. Turbulent mixing combined with a polymer stabilizer produces particles in the 100 nm size range, ideal for passive targeting of tumors and advantageous to increase solubility. We have used FNP to create nanoparticles containing a series of labile silicate prodrugs having customized hydrophobic character and hydrolysis rates.  These are stabilized with poly(ethyleneglycol)-b-poly(lactic-co-glycolic acid) with well controlled molecular weights and narrow polydispersities.  The particles are highly loaded and release studies indicate that hydrolysis occurs inside the particles with the drug released at rates controlled by the stereoelectronic character of the silicate.  A 4T1 (breast cancer) cell culture assay demonstrated in vitro efficacy.  In vivo studies will be reported.