Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.

Authors

  • Tomoaki Kurosaki Nagasaki University Hospital
  • Takashi Kitahara Nagasaki University Hospital
  • Mugen Teshima Nagasaki University Hospital
  • Koyo Nishida Course of Medical and Dental Sciences
  • Junzo Nakamura Course of Medical and Dental Sciences
  • Mikiro Nakashima Course of Medical and Dental Sciences
  • Hideto To Nagasaki University Hospital
  • Hiromitsu Hukuchi Nagasaki University Hospital
  • Tomoyuki Hamamoto Nagasaki University Hospital
  • Hitoshi Sasaki Nagasaki University Hospital

DOI:

https://doi.org/10.18433/J31S3B

Abstract

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

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Author Biographies

Tomoaki Kurosaki, Nagasaki University Hospital

Department of Hospital Pharmacy

Takashi Kitahara, Nagasaki University Hospital

Department of Hospital Pharmacy

Hitoshi Sasaki, Nagasaki University Hospital

Department of Hospital Pharmacy

Published

2009-01-05

How to Cite

Kurosaki, T., Kitahara, T., Teshima, M., Nishida, K., Nakamura, J., Nakashima, M., … Sasaki, H. (2009). Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. Journal of Pharmacy & Pharmaceutical Sciences, 11(4), 56–67. https://doi.org/10.18433/J31S3B

Issue

Section

Pharmaceutical Sciences; Original Research Articles