Design and preparation of naringenin loaded functional biomimetic nano-drug delivery system for Alzheimer’s disease

Abstract

Efficient brain drug delivery has been a challenge in the treatment of Alzheimer’s Disease and other brain disorders as blood-brain barrier (BBB) impedes most drugs to reach brain. To overcome this obstacle, we developed a novel TGN decorated erythrocyte membrane-coated poly (lactic-co-glycolic acid) nanoparticle (TRNNs). The nanoparticle significantly boosted the penetration (7.3 times) in a U-118MG and HCMEC/D3 cell co-culture BBB model in vitro. Living image was performed to assess the TRNNs distribution in vivo. The fluorescence intensity in the isolated brain of TRDNs-treated mice was about 8 times that of the DNs-treated. In the novel object recognition test, the mice after administration of TRDNs showed higher recognition index (0.414 ± 0.016) than the model group (0.275 ± 0.019). A significant increase in the number of dendritic spines from TRNNs administrated mice hippocampi neurons was observed after Golgi stain. This improvement of neurons was also confirmed by the significant high expression of PSD95 protein level in hippocampi. We measured the OD values of Aβ_25-35 induced PC12 cells that pre-treatment with different nanoparticles and concluded that TRNNs had a robust neuroprotection effect. Above all, functional biomimetic nanoparticles could increase the accumulation of naringenin into brain, thereby enable the drug to exert greater therapeutic effects.

Keywords:

• Naringenin
• brain-targeted peptide
• Alzheimer’s disease
• blood-brain barrier
• nano drug delivery system

Acknowledgements

The authors were grateful to Yitong Wang and Ao Xue of Heilongjiang University of Chinese Medicine for their assistance in living image and western blot analysis.

Author contributions

Conceptualisation, C.Y., F.G., N.Z. and X.W; writing – original draft preparation, C.Y., J.G., S.Y., and H.W.; writing – review and editing, C.Y., F.G. and X.L. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Natural Science Foundation of Heilongjiang Province [grant number LH2023H050], National Natural Science Foundation of China [grant number 82174007], Scientific Research of Harbin Normal University [grant number XPPY202206], and General project of scientific research project of Wuxi Municipal Health Commission [M202206].