Nanotech Revolution for the Anti-Cancer Drug Delivery through Blood- Brain-Barrier

M.      Caraglia; G.      De Rosa; G.      Salzano; D.      Santini; M.      Lamberti; P.      Sperlongano; A.      Lombardi; A.      Abbruzzese; R.      Addeo

Abstract

Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

Keywords: Brain delivery, drug delivery, drug targeting, liposomes, nanoparticles, tumour, blood-brain barrier, polyethylenglicol, reticulo-endothelial system, multidrug resistant protein, Tempamine, lactoferrin, excitatory amino acid transporter, receptor-mediated transcytosis