Disclosed are a brain-targeted delivery system for carrier-free nasal nano preparation modified by chitosan oligosaccharide and a preparation method therefor. The system comprises a neuroprotective hydrophobic micro-molecule drug, a polyethylene glycol derivative, and chitosan oligosaccharide. Further provided is a preparation method for the brain-targeted delivery system for nasal nano preparation. The preparation method comprises the following steps: step 1, preparing freeze-dried nano-particle powder; and step 2, stirring the freeze-dried powder and chitosan oligosaccharide in isotonic normal saline before use to form a nasal preparation having good membrane permeability. The preparation method for the system is simple, and can improve the hydrophobicity of the micro-molecule drug, reduce the toxicity and enhance the neuroprotective effect. The system is free of carriers, and avoids biodegradation problems and accumulative toxin. The drug carrying rate reaches 25 percent or above, the membrane permeability and absorption performance are good after modification by chitosan oligosaccharide, and the drug is delivered into the brain with high targeting property. The dosage form is applied by means of nasal dripping, spray and the like, and the application operation is simple, thereby facilitating patients who use the drug for a long time, and bringing good application prospect in the treatment of nervous system diseases.
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