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Curcumin is a natural component extracted  from 
rhizomes  of  turmeric with a wide range of beneficial
neuro-protective functions  include  anti-inflammatory, antioxidant , metal
chelating and anti-Ab-aggregation activities(1). Curcumin 
as  a promising new natural
sabstance, 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, rapid
metabolism and systemic elimination, its plasma concentration is very low. Furthermore,
because of  the specific properties of
blood–brain barrier(BBB), only traces of curcumin were transported across BBB(5, 6). Several approaches have
been attempted to increase curcumin bioavailability by using adjuvants such as
piperine, liposomal curcumin, and curcumin loaded polymeric nanoparticles (7, 8). Using
biodegradable nanoparticle is an excellent approach to enhance curcumin
bioavailability in the brain (9, 10). Lipid nanoparticles as one of the promising
drug delivery system(DDS) offer an attractive means of drug delivery which have
recently found as a potential approach for brain
targeting because of their lipidic nature(11). Solid
lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a class of colloidal carriers with low toxicity. They possess the advantages of
liposomes and polymeric nanoparticles, without having their shortcomings such
as scaling-up difficulties, high cost of raw materials, complicated
production process, physical instability of liposomes, and probability of
monomers toxicity in the case of polymeric nanoparticles(12, 13). Being solid at
room and body temperature, these nano-sized biocompatible lipid-based carriers
can control the drug release and can be used all routes of administration(14, 15). Some of the popular surfactants using in lipid nanoparticles
production such as Tween 80  possess P-gp
inhibitory 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-coated
nanoparticles mimic the low density lipoprotein (LDL) particles and can
interact with the LDL receptor which leads their uptake by the endothelial
cells. 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 lipid
nanoparticle preparation. The high shear homogenization-ultrasonication method is
one 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 average
particle sizes in the range of 100–200 nm. In this work, our main goal was to
design a lipidic nanocariiers in order to improve brain curcumin uptake. First,
the factors which affect preparation of Curcumine-loaded solid lipid
nanoparticles (Cur-SLNs) have been optimized. Then, for attaining the optimum
condition with a high drug payload and decreased particle size, the effect of
liquid lipid and cholesterol was examined on the formulation. Eventually we
have reached to curcumin-loaded nanostructured lipid carriers (Cur- NLCs) as an
effective nanoparticles for brain drug delivery. It should be noted that the
factorial designs have been applied in order to observe the effect of process
variables alteration on the physicochemical properties of the lipid
nanoparticles. 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,we
have used desirability  functions in
a  process  known 
as  multi-objective  optimization 
(MOO)  to. MOO was utilized
because 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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