We found good affinity between polysorbate 80 and DZP-CHP, with mean ± SD coverage 2.7 ± 0.372. DZP-CHP nanoparticles prepared with the optimal feed ratio (DZP : CHP = 1 : 5) were coated with polysorbate 80, and the adsorption process was determined by isothermal titration calorimetry. On dynamic light-scattering measurement, mean ± SD particle size was 260.7 ± 1.76 nm, polydispersity index 0.123 ± 0.004, and zeta potential −5.75 ± 0.64 mV. The mean ± SD drug loading and entrapment efficiency were high: 13.52 ± 2.03 and 86.54 ± 1.31. We determined the drug loading and encapsulation efficiency of DZP-CHP nanoparticles at different feed ratios. In this study, we prepared donepezil drug-loaded nanoparticles (DZP) with cholesterol-modified pullulan (CHP) as the nanocarrier (DZP-CHP) and surface modified the drug-loaded nanoparticles to improve the water solubility of donepezil while enhancing its targeting and sustained release. Most free drugs that cross the blood–brain barrier are characterized by high liposolubility, but they often have limited clinical applications because of poor dissolution and poor bioavailability.
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