Development of novel and multifunctional polymeric nanoparticles for brain targeted drug delivery

Abstract

Controlled release systems have become an innovative technique to treat diseases like cancer by the targeted delivery to individual cells and tissues. There is an urgent need to achieve efficacious and safe delivery with minimal nonspecific uptake by healthy tissues. Among the polymer-based nanoparticulate systems for drug delivery, nanoparticles (NPs) have represented a promising opportunity as delivery system due to their degradation in water-soluble compounds that enter the normal metabolic pathways of the organism and their capacity to modify pharmacokinetics and the drug tissue distribution profile. An engineered and versatile targeted nano-platform for the delivery of paclitaxel (PTX) across the blood brain barrier (BBB) with the aim to improve its therapeutic effect on human glioma cells has been developed. A novel biodegradable polymer has been synthetized and custom tailored NPs have been obtained. The method allows to modify the targeted drug delivery for efficiently transport and release of active drug molecule across the BBB. Aiming a dual targeting strategy, functionalization with ligands known to be efficiently transported across BBB by a membrane receptor that also is over-expressed on human glioma cells has been employed to shuttle PTX from blood to brain and then target glioma cells. In vivo properties of the NPs have been explored to assess their biological profile and since the pressing need for careful evaluation, new strategies for NPs radiolabeling with the aim to investigate their in vivo fate, specifically stability in biological environments (stealthiness), biodistribution and pharmacokinetic, have been adopted.