Pharmaceutical Research

, Volume 31, Issue 5, pp 1194–1209

Influence of Short-Chain Cell-Penetrating Peptides on Transport of Doxorubicin Encapsulating Receptor-Targeted Liposomes Across Brain Endothelial Barrier

  • Gitanjali Sharma
  • Amit Modgil
  • Tiecheng Zhong
  • Chengwen Sun
  • Jagdish Singh
Research Paper

DOI: 10.1007/s11095-013-1242-x

Cite this article as:
Sharma, G., Modgil, A., Zhong, T. et al. Pharm Res (2014) 31: 1194. doi:10.1007/s11095-013-1242-x

Abstract

Purpose

To investigate the influence of different cell penetrating peptides (CPPs-TAT, Penetratin and Mastoparan), on the transport of doxorubicin encapsulating transferrin (Tf)-liposomes across brain endothelial barrier, in vitro and in vivo.

Methods

The cellular uptake of dual-functionalized, (Tf-CPP), liposomes into various tumor cells was assessed using HPLC. The transport of liposomes was also measured across a robust 3D brain tumor model constructed using chitosan-PLGA scaffolds. The growth of tumor cells was monitored using H&E staining and the fully grown tumor scaffolds were visualized using SEM. The tumor scaffolds were combined with the culture inserts carrying tightly packed brain endothelial cells. The in vitro and in vivo transport of drug (using Tf-CPP-liposomes) across the brain endothelial barrier was determined by extraction of the drug from cells and tissues followed by analysis using HPLC.

Results

The results demonstrated improved delivery of doxorubicin using dual-functionalized liposomes versus the single ligand or unmodified liposomes. Among different Tf-CPP-liposomes, the Tf-Penetratin liposomes showed efficient cellular transport of the encapsulated drug (approximately 90–98%) and maximum translocation of the drug across the brain endothelial barrier (approximately 15% across in vitro and 4% across in vivo BBB). The Tf-Penetratin and Tf-TAT liposomes demonstrated excellent cellular biocompatibility and no hemolytic activity upto 200nM phospholipid concentration.

Conclusions

The Tf-CPP liposomes showed efficient translocation of the anticancer drug across the brain endothelial barrier. In addition, an absolute and robust in vitro brain tumor model was successfully constructed to overcome the practical intricacies of developing a successful in vivo orthotopic brain tumor model.

KEY WORDS

blood brain barrier cell penetrating peptides dual-functionalized liposomes tumor 

Supplementary material

11095_2013_1242_MOESM1_ESM.docx (1.4 mb)
ESM 1(DOCX 1.37 mb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Gitanjali Sharma
    • 1
  • Amit Modgil
    • 1
  • Tiecheng Zhong
    • 1
  • Chengwen Sun
    • 1
  • Jagdish Singh
    • 1
    • 2
  1. 1.Department of Pharmaceutical Sciences College of Pharmacy Nursing and Allied SciencesNorth Dakota State UniversityFargoUSA
  2. 2.Department of Pharmaceutical Sciences College of Pharmacy, Nursing & Allied SciencesNorth Dakota State UniversityFargoUSA