Nanodelivery of drugs for therapeutic strategies in CNS disorders. Current and Future perspectives

A. Sharma, D.F. Muresanu, J.V. Lafuente, R. Patnaik, Z.R. Tian, A. Ozikzilcik, H. Mössler, H.S. Sharma
Uppsala University,

Keywords: nanodelivery, CNS disorders, Blood-brain barrier, H-290/51, cerebrolysin


Nanodelivery of drugs, diagnostic agents and other functionalized nanoparticles aiming for better treatment of diseases or diagnosis purposes are the new trends in medicine that appear promising. However, nanoparticles or nanotechnology used to deliver these agents in vivo may have potential risks for cell and tissue damages. Thus, before nanotechnology is widely accepted as a routine therapeutic tool for effective medical treatment or for diagnostic tools this is mandatory to study their potential or plausible neurotoxic effects in details. So far effects of nanoparticles or nanomaterials including biodegradable nanoparticles on toxicity in the central nervous system (CNS) is not very well documented in the literature. Also, there is an urgent need to find dose related studies on nanoparticles on cellular toxicity especially in vivo situations. Without these details and systematic studies, the use of nanomedicine still remains questionable. There are also reports that drugs delivered through different kinds of nanoparticles, nanowires or poly-lactic-co-glycolic acid (PLGA) nanoparticles even in identical doses have slightly but significantly different effects on cellular protection when administered in vivo situations. This suggests that drug effects could vary depending on the use of specific nanocarriers. In our hands, drugs i.e., cerebrolysin, DL-3-n-butylphthalide (DL-NBP) or H-290/51 tagged with TiO2 nanowires or titanate nanospheres have superior neuroprotective effects in CNS injury than their delivered through PLGA-nanoparticles in identical manner. Although, TiO2 by itself has no cellular toxicity effects within 48 h of its administration, data on other nanoparticles on neurotoxicity in vivo is still lacking. We examined sleep deprivation (SD) induced brain pathology and therapeutic strategies using nanodelivery of cerebrolysin. SD is a serious problem in military and we have previously shown that SD of 12 to 48 h causes blood-brain barrier (BBB) disruption, brain edema formation and neuronal damages. We found significant increase in the BBB disruption, brain edema formation and neuronal injuries after 48 h SD. Measurement of BDNF showed 50 to 60 % decline in different brain areas in SD Nanowired delivery of cerebrolysin 4 to 6 h after the onset of SD significantly reduced brain pathology and enhanced regional BDNF levels after 48 h SD. However, normal cerebrolysin given after the onset of SD has only minimal effects on regional BDNF level and brain pathology seen at 48 h. This indicates that nanodelivery of drugs have superior effects in achieving neuroprotection. Thus, we feel that our policy makers, researchers, clinicians and nanotechnologists should consider exploring the dose response relationship of nanoparticles from wide variety of nanocarriers on cellular toxicity in both vivo and in vitro situation urgently. These studies will help create a database for suitable nanocarriers to use for drug delivery to the CNS as effective therapeutic tools in clinics. Only after these data nanoneuropharmacology is developed as a distinct discipline in future