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AAPS PharmSciTech

, 20:50 | Cite as

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

  • Manit Gandhi
  • Priyanka Bhatt
  • Gaurav Chauhan
  • Sarita Gupta
  • Ambikanandan Misra
  • Rajashree MashruEmail author
Research Article Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems
  • 121 Downloads
Part of the following topical collections:
  1. Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems

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.

KEY WORDS

gene therapy depression CNS targeting liposomes p11 gene 

Notes

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.

Compliance with Ethical Standards

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.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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High resolution image (TIF 135 kb)
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Supplementary file 2

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High resolution image (TIF 113 kb)
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Supplementary file 3 (PNG 62 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Manit Gandhi
    • 1
  • Priyanka Bhatt
    • 1
  • Gaurav Chauhan
    • 1
  • Sarita Gupta
    • 1
  • Ambikanandan Misra
    • 1
  • Rajashree Mashru
    • 1
    Email author
  1. 1.Pharmacy Department, Faculty of Technology and EngineeringThe Maharaja Sayajirao University of BarodaVadodaraIndia

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