Bioinspired lipid-polysaccharide modified hybrid nanoparticles as a brain-targeted highly loaded carrier for a...

Lipid-polysaccharide modified biohybrid nanoparticles (NPs) are eminent drug carriers for brain targeting, owing to their ability to prolong the circulation time and penetrate the blood brain barrier (BBB). Biohybrid NPs particular interest arises from their potential to mimic biological components. Herein, we prepared bioinspired lipid polymeric NPs, either naked or surface modified by a synthesized biocompatible dextran-cholic acid (DxC). The nanoprecipitation method was tailored to allow the assembly of the multicomponent NPs in a single step. Modulating the solvent/antisolvent system provided lipid polymer hybrid NPs in the size of 111.6 ± 11.4 nm size. The NPs encapsulated up to 92 ± 1.2% of a hydrophilic anti-Alzheimer drug, rivastigmine (Riv). The brain uptake, biodistribution and pharmacokinetics studies, proved the efficient fast penetration of the bioinspired surface modified NPs to the brain of healthy albino rats. The modified nanocarrier caused a 5.4 fold increase in brain targeting efficiency compared to the drug solution. Furthermore, the presence of DxC increased Riv's brain residence time up to 40 h. The achieved results suggest that the fabricated biohybrid delivery system was able to circumvent the BBB and is expected to minimize Riv systemic side effects.