Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation.
Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4180071?pdf=render |
| _version_ | 1811290846918606848 |
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| author | Tsukasa Shigehiro Tomonari Kasai Masaharu Murakami Sreeja C Sekhar Yuki Tominaga Masashi Okada Takayuki Kudoh Akifumi Mizutani Hiroshi Murakami David S Salomon Katsuhiko Mikuni Tadakatsu Mandai Hiroki Hamada Masaharu Seno |
| author_facet | Tsukasa Shigehiro Tomonari Kasai Masaharu Murakami Sreeja C Sekhar Yuki Tominaga Masashi Okada Takayuki Kudoh Akifumi Mizutani Hiroshi Murakami David S Salomon Katsuhiko Mikuni Tadakatsu Mandai Hiroki Hamada Masaharu Seno |
| author_sort | Tsukasa Shigehiro |
| collection | DOAJ |
| description | Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside. |
| first_indexed | 2024-04-13T04:20:34Z |
| format | Article |
| id | doaj.art-9d70f1e49e4445e788735539da75532b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T04:20:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9d70f1e49e4445e788735539da75532b2022-12-22T03:02:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10797610.1371/journal.pone.0107976Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation.Tsukasa ShigehiroTomonari KasaiMasaharu MurakamiSreeja C SekharYuki TominagaMasashi OkadaTakayuki KudohAkifumi MizutaniHiroshi MurakamiDavid S SalomonKatsuhiko MikuniTadakatsu MandaiHiroki HamadaMasaharu SenoAlthough the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.http://europepmc.org/articles/PMC4180071?pdf=render |
| spellingShingle | Tsukasa Shigehiro Tomonari Kasai Masaharu Murakami Sreeja C Sekhar Yuki Tominaga Masashi Okada Takayuki Kudoh Akifumi Mizutani Hiroshi Murakami David S Salomon Katsuhiko Mikuni Tadakatsu Mandai Hiroki Hamada Masaharu Seno Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. PLoS ONE |
| title | Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. |
| title_full | Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. |
| title_fullStr | Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. |
| title_full_unstemmed | Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. |
| title_short | Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. |
| title_sort | efficient drug delivery of paclitaxel glycoside a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation |
| url | http://europepmc.org/articles/PMC4180071?pdf=render |
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