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Curcumin is a natural component extracted  from rhizomes  of  turmeric with a wide range of beneficialneuro-protective functions  include  anti-inflammatory, antioxidant , metalchelating and anti-Ab-aggregation activities(1). Curcumin as  a promising new naturalsabstance, in  cancer  chemotherapy has antitumor  activity (2). curcmin can act as a multi therapeutic  agent and can be very useful  in a wide variety of neurodegenerative  and neurological  disorders  such as  Alzheimer’s  disease (AD), Huntington’s  disease  (HD) and Parkinson’s  disease (PD)  (3, 4) . However due to its poor absorption and stability at physiological pH, rapidmetabolism and systemic elimination, its plasma concentration is very low. Furthermore,because of  the specific properties ofblood–brain barrier(BBB), only traces of curcumin were transported across BBB(5, 6). Several approaches havebeen attempted to increase curcumin bioavailability by using adjuvants such aspiperine, liposomal curcumin, and curcumin loaded polymeric nanoparticles (7, 8). Usingbiodegradable nanoparticle is an excellent approach to enhance curcuminbioavailability in the brain (9, 10). Lipid nanoparticles as one of the promisingdrug delivery system(DDS) offer an attractive means of drug delivery which haverecently found as a potential approach for braintargeting because of their lipidic nature(11).

Solidlipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a class of colloidal carriers with low toxicity. They possess the advantages ofliposomes and polymeric nanoparticles, without having their shortcomings suchas scaling-up difficulties, high cost of raw materials, complicatedproduction process, physical instability of liposomes, and probability ofmonomers toxicity in the case of polymeric nanoparticles(12, 13). Being solid atroom and body temperature, these nano-sized biocompatible lipid-based carrierscan control the drug release and can be used all routes of administration(14, 15). Some of the popular surfactants using in lipid nanoparticlesproduction such as Tween 80  possess P-gpinhibitory effects(16). Moreover many studies  have  revealed that  Tween 80 can  induce apolipoprotein  E  (apoE) adsorption  onto the  nanoparticle’s  surface. It seems that the  apoE-coatednanoparticles mimic the low density lipoprotein (LDL) particles and caninteract with the LDL receptor which leads their uptake by the endothelialcells.

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One of the most effective ways for improving brain  drug delivery is using LDL receptors (17, 18). A variety of techniques have been developed for lipidnanoparticle preparation. The high shear homogenization-ultrasonication method isone of the first techniques that has attracted great attention in recent years (19-22).The benefits of this technique include the simplicity and ease of handling (20, 22) low polydispersity index (PI) usually below 0.3 and averageparticle sizes in the range of 100–200 nm.

In this work, our main goal was todesign a lipidic nanocariiers in order to improve brain curcumin uptake. First,the factors which affect preparation of Curcumine-loaded solid lipidnanoparticles (Cur-SLNs) have been optimized. Then, for attaining the optimumcondition with a high drug payload and decreased particle size, the effect ofliquid lipid and cholesterol was examined on the formulation. Eventually wehave reached to curcumin-loaded nanostructured lipid carriers (Cur- NLCs) as aneffective nanoparticles for brain drug delivery.

It should be noted that thefactorial designs have been applied in order to observe the effect of processvariables alteration on the physicochemical properties of the lipidnanoparticles. Obtaining  an  optimal procedure  requires  different dependent and  independent  variables to  be  simultaneously  set. For finding the most  effective variables  and observing possible factor interactions,wehave used desirability  functions ina  process  known as  multi-objective  optimization (MOO)  to. MOO was utilizedbecause of its high sensitivity to interactions between two or three factors,explaining their effects on the characteristics of curcumin lipid nanoparticles(23, 24). Finlly,  a  series of  in  vitro characterization tests and in vivo investigations were  carried out  on  the prepared lipid nanoparticles to evaluate their  potency

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