Development of multifunctional polymeric nanoparticles as advanced delivery systems targeting the blood-brain barrier

Abstract

Multifunctional polymeric nanoparticles (NP) represent a promising alternative for the treatment of neurodegenerative diseases using the intravenous route (i.v.) [1]. In current treatments, the effects of the intravenously injected drugs are systemic, thus causing severe side effects. NP can act specifically in a tissue provided that they are properly designed [2]. To target the central nervous system (CNS), a targeting moiety is required to cross the blood-brain barrier (BBB), which is a current key goal under intense investigations [3]. An interesting approach is the use of polymeric NP as nonviral gene delivery systems, since they can protect and direct genes through the BBB, as well as their use as drug delivery systems [4]. The aim of this work was to obtain multifunctional polymeric NP as advanced delivery systems able to cross the BBB. Polymeric NP were obtained by nano-emulsion (NE) templating, using poly(lactic-coglycolic acid) (PLGA), by the solvent evaporation method [5]. O/W polymeric NE were prepared by a low-energy method, the phase inversion composition method (PIC) [6]. Polymeric NP with appropriate sizes for the i.v. administration (<1 m) were obtained. A model fluorescent, and analgesic and antiapoptotic drugs were successfully encapsulated into PLGA NP. In addition, their surface was functionalized using various elements (e.g. a monoclonal antibody or antisense oligonucleotides). In vitro tests showed that formulated NP are non-toxic, weak activators of the immune system and they enhance gene transfection in cell cultures. In vivo tests confirmed that antibodyfunctionalized NP are able to cross the BBB.