Formulation development of tocopherol polyethylene glycol nanoengineered polyamidoamine dendrimer for neuroprotection and treatment of Alzheimer disease

Abstract

Amyloid-beta (Aβ) aggregates deposition at extra neuronal sites induces neurotoxicity and major hallmarks of Alzheimer’s disease (AD). To reduce the Aβ fibril toxicity, multi-functional polyamidoamine (PAMAM) dendrimer was conjugated with tocopheryl polyethylene glycol succinate-1000 (TPGS) which acts as a carrier matrix for the delivery of neuroprotective molecule piperine (PIP). This PIP-TPGS-PAMAM dendrimer was fabricated to mitigate the Aβ_1–42 fibril toxicity on SHSY5Y cells. TPGS-PAMAM was fabricated through carbodiimide coupling reaction, and PIP was encapsulated in dendrimer through solvent injection method to prepare PIP-TPGS-PAMAM. Antioxidant assay of PIP-TPGS-PAMAM showed 90.18% inhibition of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals compared to free PIP, which was 28.27%. The SHSY5Y cells showed 37.25% for negative control group and 82.55% cell viability for PIP-TPGS-PAMAM treated group against Aβ_1–42 toxicity. PIP-TPGS-PAMAM reduced the ROS activity to 15.21% and 48.5% for free PIP treated in cell group. Similarly, extent of Aβ_1-42-induced apoptosis also reduced significantly from 38.2% to 12.36% in PIP-TPGS-PAMAM treated group. In addition, PIP-TPGS-PAMAM also disaggregated the Aβ_1–42 fibril in SHSY5Y cells. Our findings suggested that PIP-TPGS-PAMAM showed mitigation of Aβ_1-42-induced toxicity in neuronal cells, which can offer excellent prospect of neuroprotection and AD therapy.

Keywords:

• Polyamidoamine dendrimer
• tocopheryl polyethylene glycol succinate
• piperine
• amyloid
• neuroprotection
• Alzheimer disease

Acknowledgements

The authors thank the Department Pharmaceuticals (DOP) under the ministry of chemicals and fertilisers, the Govt of India, for providing research facilities and funding. NIPER-R communication/212.

Author contributions

All authors have given permission for the final version of the manuscript.

Disclosure statement

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