Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.
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. Method...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2009-01-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/1623 |
| _version_ | 1827163830774398976 |
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| author | Tomoaki Kurosaki Takashi Kitahara Mugen Teshima Koyo Nishida Junzo Nakamura Mikiro Nakashima Hideto To Hiromitsu Hukuchi Tomoyuki Hamamoto Hitoshi Sasaki |
| author_facet | Tomoaki Kurosaki Takashi Kitahara Mugen Teshima Koyo Nishida Junzo Nakamura Mikiro Nakashima Hideto To Hiromitsu Hukuchi Tomoyuki Hamamoto Hitoshi Sasaki |
| author_sort | Tomoaki Kurosaki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:19:33Z |
| format | Article |
| id | doaj.art-389b5a1c1d534229b018f89336765923 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2025-03-21T01:06:57Z |
| publishDate | 2009-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-389b5a1c1d534229b018f893367659232024-08-03T03:22:53ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262009-01-0111410.18433/J31S3BExploitation of De Novo Helper-Lipids for Effective Gene Delivery.Tomoaki Kurosaki0Takashi Kitahara1Mugen Teshima2Koyo Nishida3Junzo Nakamura4Mikiro Nakashima5Hideto To6Hiromitsu Hukuchi7Tomoyuki Hamamoto8Hitoshi Sasaki9Nagasaki University HospitalNagasaki University HospitalNagasaki University HospitalCourse of Medical and Dental SciencesCourse of Medical and Dental SciencesCourse of Medical and Dental SciencesNagasaki University HospitalNagasaki University HospitalNagasaki University HospitalNagasaki University HospitalPurpose: 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.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/1623 |
| spellingShingle | Tomoaki Kurosaki Takashi Kitahara Mugen Teshima Koyo Nishida Junzo Nakamura Mikiro Nakashima Hideto To Hiromitsu Hukuchi Tomoyuki Hamamoto Hitoshi Sasaki Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. Journal of Pharmacy & Pharmaceutical Sciences |
| title | Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. |
| title_full | Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. |
| title_fullStr | Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. |
| title_full_unstemmed | Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. |
| title_short | Exploitation of De Novo Helper-Lipids for Effective Gene Delivery. |
| title_sort | exploitation of de novo helper lipids for effective gene delivery |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/1623 |
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