Brain targeting by engineered nanoparticles

In the last years, the application of "nanotechnology“ to the field of “medicine” surely represented the most innovative strategy to cope with difficult-to-treat diseases. Thus, nanotech-based drug delivery and targeting are nowadays some of the hottest topics in science and in particular in Neuroscience. The results of our research, based on in vitro and in vivo preclinical tests strongly indicate that specifically engineered nanoparticles, made of poly-lactide-co-glycolide (PLGA) polymer, are able to cross the Blood-brain barrier (BBB) and to deliver a variety of drugs or active molecules inside the Central Nervous System (CNS). A recent report from the World Health Organization (WHO) emphasizes that neurological disorders (brain injuries, neuroinfections, multiple sclerosis, epilepsy, stroke, Alzheimer and Parkinson disease) affect up to one billion people worldwide [World Health Organization, Neurological disorders : public health challenger, Geneva, 2006]. Until now, only 2% of the overall drugs are able to enter the brain as the BBB restricts the diffusion of substances from blood to the brain. Thus, one of the challenges of pharmaceutical research nowadays is to discover tools enabling an effective and efficacious delivery of drugs into the CNS. To improve the efficacy of drugs, a possible answer could be the nanomedicine approach, and its application on neuroscience (neuro-nanomedicine). Thereby, the perspective of introducing a tool, capable of directed delivery of every drug into the brain, is undoubtedly an attractive goal for researchers and practitioners. To that end, neuro -nanomedicine exploits pharmaceutical technology, using well-known nanocarriers such as liposomes and polymeric nanoparticles (NPs). These nanosystems, ranging from 100 nm to 250 nm, are able to protect loaded drugs from being metabolised and eliminated, to assure the controlled release of the embedded drugs and to target specific cell population if specifically engineered.To achieve this goal we planned, create and test specifically engineering the NPs surface able to take advantage of the BBB crossing pathways, such as endocytosis or transcytosis. We applied this approach modifying FDA-approved biodegradable NPs with two different peptides to produce highly selective nanosystems able to enter the brain after i.v. administration in the rodents model. The administration of engineered-NPs allowed a variety of drugs to cross the BBB at a rate of 15-20% of the injected dose. The mechanism of BBB crossing of those NPs were elucidated by means of several in vitro and in vivo experiments as the safety of NPs on neuron cell colture was proven. The potential impact of such nanotech-based innovations relies on the possible changes in treatments and cures of the most difficult-to-treat neurological diseases, opening the pave to a new vista on the future trend in medicine, which should strengthen the relationship between different field of research (from clinician-based to chemistry, nanotechnology, biology and pre-clinical study) becoming more and more translational and interdisciplinar.