IGF-II-Conjugated Nanocarrier for Brain-Targeted Delivery of p11 Gene for Depression

Abstract

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors. They were further converted using IGF-II mAb into immunoliposomes for CNS targeting and mAb conjugation to liposomes were characterised by SDS-PAGE. They were further analysed by in vitro characterisation studies that include erythrocyte aggregation study, electrolyte-induced study, heparin compatibility study and serum stability studies. SHSY5Y cells were used for conducting cytotoxicity of synthesised lipids and live imaging of cell uptake for 25 min. Finally, the brain distribution studies and western blot were carried out in animals to evaluate them for their BBB permeation ability and effects on p11 protein which is believed to be a culprit. These formulated liposomes from synthesised lipids offer a promising approach for the treatment of depression.

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Acknowledgments

The authors would like to thank the Department of Chemistry and Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, for the help in carrying out lipid synthesis and plasmid isolation respectively.

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Correspondence to Rajashree Mashru.

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The protocol for the study was duly approved by Institutional Animal Ethics Committee, Faculty of Pharmacy, The M. S. University of Baroda, Vadodara, vide protocol approval no: MSU/IAEC/2016-17/1631.

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The authors declare that they have no conflict of interest.

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Gandhi, M., Bhatt, P., Chauhan, G. et al. IGF-II-Conjugated Nanocarrier for Brain-Targeted Delivery of p11 Gene for Depression. AAPS PharmSciTech 20, 50 (2019). https://doi.org/10.1208/s12249-018-1206-x

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KEY WORDS

  • gene therapy
  • depression
  • CNS targeting
  • liposomes
  • p11 gene