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Techniques to transport neurotherapeutics to brain Broadly these approaches can be classified as invasive methods or the non-invasive methods.Invasive methods deliver drug locally into CNS by physically crossing the BBB. Parenchyma of brain is targeted by intracerebroventricular injection into CSF. Enhanced penetration of the medications is by the transient disintegration of BBB either by magnetic resonance, osmotic obstruction or by the use of focussed imaging disruption. But this approach is used only under the extreme state of treatment, because • It necessitates expertise, accuracy and precision. • It is not economic to the patient requires hospitalization.• It has some unwanted effects like physiological stress and abnormal increase in the intracranial pressure.Non-invasive methods acquire extensive drug distribution by using network of blood vessels in brain. Conventionally intravenous administration is employed to deliver NT, but now a days transnasal administration via olfactory or trigeminal neuronal path is being used widely. This has several advantages as• It directly delivers NT to brain by overcoming the BBB, reducing first pass metabolism and systemic dilution.• Use of Absorption enhancers and mucoadhesives increase the residence duration by overcoming the mucociliary clearance, enzymatic degradation or the barriers imposed by epithelium and the mucus layer.Methods of nanoparticles uptake across the blood brain barrierThe mechanisms responsible for internalizing the particles are transcytosis or transcellular routes which are broadly classified into Absorptive-mediated transcytosis that involves non-specific interaction of the particles to the membranes of the cell via plasmalemmal vesicles (caveolae) or clathrin coated pits. There is also the possibility of caveolae-clathrin independent endocytosis.Receptor mediated endocytosis where the larger molecules are taken by specific receptors that are present in special transport vesicles involved in endocytosis. These receptors entail transferrin receptors, insulin receptors and the low density lipoprotein receptor related proteins.Nano-emulsion based formulations overcoming blood brain barrier for CNS disorders Treatment of Central nervous system related diseases is usually cumbersome owing to incapability of the medications to escape the blood brain barrier, blood-CSF barrier, and effluxtransporters. So regular treatments have largely been replaced by the advanced nano technological procedures such as nano-emulsion via different administration routes. And among them intranasal route is used most commonly. As it is the non-invasive way to transport the medicine directly to the CNS. Here are some of the Nanoemulsion based formulations being used to treat neurodegenerative ailments.Cationic nanoemulsion of siRNA for TNF?TNF? is responsible for neuroinflammatory signalling that aggravates the pathological process for conditions like Huntington’s disease, epilepsy, Alzheimer’s disease, Parkinson’s disease and others. Its levels have been decreased by the use of siRNA in a cationic nanoemulsion of omega-3 fatty acids containing flaxseed oil, by the intranasal administration. In the formulation DOTAP lipid is used because of its cationic nature that facilitates higher exposure by increased mucosal residence duration, increased loading capacity and complexation with the negatively charged biomolecules, for enhanced intracellular transport. Particle size for the nanoemulsion is <400nm that provide increased surface area for absorption and interaction in olfactoryepithelium.Squanavir nanoemulsion for HIV virusHIV virus has the ability to reside inside the CNS that made the currently available anti-HIV drugs less effective. As they are not able to cross the blood brain barrier due to their less permeability so cannot completely remove the pathogen from body.cns distribution and oral bioavailability of the protease inhibitor squanavir is increased by the nanoemulsion formulation containing polyunsaturated fatty acids (PUFA) as the internal oil phase and the external consist of mixture of lipoid-80 and deoxycholic acid. Particle size of the oil droplets is in 100-200nm range. Reduced particle size and lipophilic nature enhanced permeability across the barrier and solved the problem.Nanoemulsion based antiepileptic drugs Compromised efficacy of the antiepileptic drug olanzapine due to the blood brain barrier can be enhanced by the olanzapine loaded nanoemulsion preparation delivered through intranasal route. Also the nanoemulsion preparation loaded with carbamazepine and stabilized by 1-O-alkylglycerol or lecithin demonstrated improved availability and site specific delivery on intranasal delivery, in treating generalized tonic clonic seizures. Mucoadhesive nanoemulsion loaded with risperidone administered by intranasal route shows direct delivery to the brain bypassing the barrier with enhanced efficacy and bioavailability.Ropinirole nanoemulsion for Parkinson's disease Antiparkinson's agent ropinirole has increased BBB permeability and brain translocation in nanoemulsion formulation administered by intranasal route. 36

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