Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids
Atorvastatin (ATV) has attracted considerable attention as a potential therapeutic agent for cancer because it inhibits cancer cell proliferation by suppressing the mevalonate pathway. However, because of its low oral absorption, high doses of ATV are required for chemotherapeutic applications. In t...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2149896 |
| _version_ | 1828093111685873664 |
|---|---|
| author | Laxman Subedi Prashant Pandey Bikram Khadka Jung-Hyun Shim Seung-Sik Cho Seho Kweon Youngro Byun Ki-Taek Kim Jin Woo Park |
| author_facet | Laxman Subedi Prashant Pandey Bikram Khadka Jung-Hyun Shim Seung-Sik Cho Seho Kweon Youngro Byun Ki-Taek Kim Jin Woo Park |
| author_sort | Laxman Subedi |
| collection | DOAJ |
| description | Atorvastatin (ATV) has attracted considerable attention as a potential therapeutic agent for cancer because it inhibits cancer cell proliferation by suppressing the mevalonate pathway. However, because of its low oral absorption, high doses of ATV are required for chemotherapeutic applications. In this study, we constructed ATV-loaded nanoemulsions (ATV-NEs) containing multivalent intestinal transporter-targeting lipids to improve the oral bioavailability of ATV. ATV-NEs were prepared via oil-in-water emulsification for transporter-targeted delivery, and contained the following anchors: an ionic complex of deoxycholic acid (DOCA) with the cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP), a biotin-conjugated lipid (Biotinyl PE), and d-alpha-tocopherol polyethylene glycol succinate (TPGS) to allow bile acid- and multivitamin transporter-mediated permeation of ATV without P-glycoprotein (P-gp)-mediated efflux. The optimized formulation (ATV-NE#6) had 1,091% higher oral bioavailability than free ATV. Finally, treatment of 4T1 cell-bearing mice with oral ATV-NE#6 (equivalent to 40 mg/kg ATV) significantly suppressed tumor growth; the maximum tumor growth reduction was 2.44-fold that of the control group. The results thus suggest that ATV-NEs allow for effective oral chemotherapy by enhancing the oral bioavailability of ATV. |
| first_indexed | 2024-04-11T06:38:27Z |
| format | Article |
| id | doaj.art-b9f9d49b1b034d44915b39b6b62ad936 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-11T06:38:27Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-b9f9d49b1b034d44915b39b6b62ad9362022-12-22T04:39:36ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012913397341310.1080/10717544.2022.2149896Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipidsLaxman Subedi0Prashant Pandey1Bikram Khadka2Jung-Hyun Shim3Seung-Sik Cho4Seho Kweon5Youngro Byun6Ki-Taek Kim7Jin Woo Park8Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaDepartment of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaAtorvastatin (ATV) has attracted considerable attention as a potential therapeutic agent for cancer because it inhibits cancer cell proliferation by suppressing the mevalonate pathway. However, because of its low oral absorption, high doses of ATV are required for chemotherapeutic applications. In this study, we constructed ATV-loaded nanoemulsions (ATV-NEs) containing multivalent intestinal transporter-targeting lipids to improve the oral bioavailability of ATV. ATV-NEs were prepared via oil-in-water emulsification for transporter-targeted delivery, and contained the following anchors: an ionic complex of deoxycholic acid (DOCA) with the cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP), a biotin-conjugated lipid (Biotinyl PE), and d-alpha-tocopherol polyethylene glycol succinate (TPGS) to allow bile acid- and multivitamin transporter-mediated permeation of ATV without P-glycoprotein (P-gp)-mediated efflux. The optimized formulation (ATV-NE#6) had 1,091% higher oral bioavailability than free ATV. Finally, treatment of 4T1 cell-bearing mice with oral ATV-NE#6 (equivalent to 40 mg/kg ATV) significantly suppressed tumor growth; the maximum tumor growth reduction was 2.44-fold that of the control group. The results thus suggest that ATV-NEs allow for effective oral chemotherapy by enhancing the oral bioavailability of ATV.https://www.tandfonline.com/doi/10.1080/10717544.2022.2149896Atorvastatinnanoemulsionbile acid-mediated uptakemultivitamin-facilitated transportoral bioavailabilityoral chemotherapy |
| spellingShingle | Laxman Subedi Prashant Pandey Bikram Khadka Jung-Hyun Shim Seung-Sik Cho Seho Kweon Youngro Byun Ki-Taek Kim Jin Woo Park Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids Drug Delivery Atorvastatin nanoemulsion bile acid-mediated uptake multivitamin-facilitated transport oral bioavailability oral chemotherapy |
| title | Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids |
| title_full | Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids |
| title_fullStr | Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids |
| title_full_unstemmed | Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids |
| title_short | Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids |
| title_sort | enhancement of the anticancer effect of atorvastatin loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter targeting lipids |
| topic | Atorvastatin nanoemulsion bile acid-mediated uptake multivitamin-facilitated transport oral bioavailability oral chemotherapy |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2149896 |
| work_keys_str_mv | AT laxmansubedi enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT prashantpandey enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT bikramkhadka enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT junghyunshim enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT seungsikcho enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT sehokweon enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT youngrobyun enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT kitaekkim enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids AT jinwoopark enhancementoftheanticancereffectofatorvastatinloadednanoemulsionsbyimprovingoralabsorptionviamultivalentintestinaltransportertargetinglipids |