Nanoparticles for treating brain cancer REALIZED BY: EL MANSOURI ABDESSAMAD SUPERVISED BY: Pr AAMOUUCH

PLAN INTRODUCTION * Molecular physiology of the BBB * Diseas related to BBB THE BLOOD BREAN BARRIER DRUG DELIVERY TO THE BRAIN COLLOIDAL CARRIERES CONCLUSION * MATERAIALS USED * MECHANISM OF TRANSAPORT * TARGETTING NANOPATRICLES 06 * Emulsion polymerization POLY(alkylcyanoacrylates) 07

INTRODUCTION

THE BLOOD BRAIN BARRIER Molecular physiology of the BBB

DRUG DELIVERY TO THE BRAIN The diffusion of a drug from the blood into the brain is mainly dependent on its ability to enter the BCECs. This is correlated with physicochemical properties such as optimised lipophilicity, low molecular size, and a neutral or negative charge, or the appropriate domain for interaction with a receptor or a carrier required to cross the BBB disrupt the BBB modify the drug characteristics use colloidal carriers

COLLOIDAL CARRIERS  Colloidal carriers consist of lipidic or polymeric particles, in which the drug is adsorbed, entrapped, or encapsulated. These include liposomes and nanoparticles.  they respond to ideal characteristics of biocompatibility, biodegradability, physical stability in the blood  they mask the drug’s physico-chemical properties USE OF COLLOIDAL DRUG CARRIERS

NANOPARTICLES The size ranging from 1 to 1000 nm and it include both ; nanocapsules (reservoir systeme) and nanospheres (a matix systeme)

NANOPARTICLES different methods developed for the preparation of nanoparticles.

EMULSION POLYMERIZATION 123 single monomer units of a given compound Once polymerization is complet e, the solution is filtered and neutralized to remove any residual monomers. Triggers for polymer grow th include high-energy radiation, UV light, or hydroxyl ions Polymerization occurs spontaneously at room temperature after initiation by either free radical or ion formation.

NANOPARTICLES Materials used Polycetates,acylic co-polymers, Poly(lactide)(PLGA) poly(alkylcyanacylates)(PACA) Poly(D-,l-lactido-glycocide)  polysobate coated nanparticles can mimic LDL to across the BBB  polyxyethylene sorbitan monooleate coated NPs containing drug easily across the BBB  Radiolabel polythylene glycole coated hexadecyanoacylate nanosphers Mechanism of transportTargetting The coating of PACA or PLGA with polysorbate 80 or polyxamer 188 The NPs adbsorb apoli poproteins E or A(-1) fr om the blood Iteract with LRP1 or wit h the scavenger recept or followed by trasytosi s across the BBB ADHESION FLUIDIZATION OF BB B ENDETHELIUM BY SURFACTANTS OPENING OF TIGHT JUNCTION TRANSCYTOSIS/END OSCYTOSis BLOCKAGE OF G LYCOPROTEIN

POLY(alkylcyanoacrylates) It’s a monomers considered as materials for biomedical applications. (PACAs) were not employed as polymers until the early 1980s. PACA NPs was coated with polysorbate 80 have been proposed to overcome the BBB and deliver drugs to the brain

POLY(alkylcyanoacrylates) MONOMER PACA

Example of this procedure ùl of monomer. PACA allowed to polymerize spontaneously for a few hours (3–4 h) under strong magnetic stirring. dispersed in acidified water containing a surfactant or a stabilizing agent (10 ml of a 0.5–1% solution of PluronThe additi on of cyclodextrins to theic F68 or dextr an 70 proat pH 2.5 adjusted with HCl). The addition of cyclodextrins to the polymerization medium can promote the association of poorly water-soluble drugs with the PACA nanos-pheres.

Disease related to BBB

CONCLUSION After 30 years of research on polymeric NPs, this delivery system practically does not exist clinically, yet NPs appear to have significant potential in delivering drugs to the brain.

Thank you FOR YOUR ATTENTION

REFERRENCES Article :GARCEL, Aude, et al. In vitro blood brain barrier models as a screening tool for colloidal drug delivery systems and other nanosystems. International Journal of Biomedical Nanoscience and Nanotechnology, 2010, vol. 1, no. 2/3/4, p Article : Targeted nanoparticles for drug delivery through the blood–brain barrier for Alzheimer’s diseaseB Article : Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier Article : Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications