Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer
Pancreatic cancer is one of the highest causes of mortality throughout the world; thus, it requires an effective treatment strategy. Some chemotherapeutic agents used in the clinics or under clinical trials are hydrophobic and have poor aqueous solubility; consequently, they also have minimal system...
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/8/778 |
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| author | Tilahun Ayane Debele Hung-Chang Wu Shang-Rung Wu Yan-Shen Shan Wen-Pin Su |
| author_facet | Tilahun Ayane Debele Hung-Chang Wu Shang-Rung Wu Yan-Shen Shan Wen-Pin Su |
| author_sort | Tilahun Ayane Debele |
| collection | DOAJ |
| description | Pancreatic cancer is one of the highest causes of mortality throughout the world; thus, it requires an effective treatment strategy. Some chemotherapeutic agents used in the clinics or under clinical trials are hydrophobic and have poor aqueous solubility; consequently, they also have minimal systemic bioavailability. Nanoparticle-based drug delivery tactics have the potential for overcoming these limitations and enhancing their therapeutic efficacy. Herein, a glutathione (GSH)-sensitive micelle (PAH-SS-PLGA) was synthesized for the combined delivery of alpha-tocopheryl succinate (TOS) and curcumin to improve its therapeutic efficacy. The chemical structures of PAH-SS-PLGA were analyzed using Proton Nuclear Magnetic Resonance (<sup>1</sup>H-NMR) and Fourier Transform Infrared (FTIR) spectroscopy, whereas the particle size, zeta potential, and surface morphology were observed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release results revealed that more TOS and curcumin were released in the presence of GSH (5 mM) than the physiological pH value. Fluorescence microscopy images revealed that nanoformulated curcumin/rhodamine was uptaken by PAN02 pancreatic cancer cells. In vitro cytotoxicity assays showed higher cytotoxicity for nanoformulated TOS and/or curcumin than free TOS and/or curcumin. In addition, higher cytotoxicity was observed for combination drugs than free drugs alone. Most interestingly, at all tested concentrations of nanoformulated drugs (PAH-SS-PLGA, TOS, and curcumin), the calculated combination index (CI) value was less than one, which shows that TOS and curcumin have a synergistic effect on cellular proliferation inhibition. Overall, synthesized co-polymers are the best carriers for combination drugs, TOS, and curcumin, because they enhance the therapeutic efficacy and improve pancreatic cancer treatments. |
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| format | Article |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:22:12Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj.art-2b0223f44b6042cd8c885bc36bcfa1c12023-11-20T10:18:19ZengMDPI AGPharmaceutics1999-49232020-08-0112877810.3390/pharmaceutics12080778Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic CancerTilahun Ayane Debele0Hung-Chang Wu1Shang-Rung Wu2Yan-Shen Shan3Wen-Pin Su4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, TaiwanDepartment of Internal Medicine, Chi Mei Medical Center, Tainan 710, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, TaiwanPancreatic cancer is one of the highest causes of mortality throughout the world; thus, it requires an effective treatment strategy. Some chemotherapeutic agents used in the clinics or under clinical trials are hydrophobic and have poor aqueous solubility; consequently, they also have minimal systemic bioavailability. Nanoparticle-based drug delivery tactics have the potential for overcoming these limitations and enhancing their therapeutic efficacy. Herein, a glutathione (GSH)-sensitive micelle (PAH-SS-PLGA) was synthesized for the combined delivery of alpha-tocopheryl succinate (TOS) and curcumin to improve its therapeutic efficacy. The chemical structures of PAH-SS-PLGA were analyzed using Proton Nuclear Magnetic Resonance (<sup>1</sup>H-NMR) and Fourier Transform Infrared (FTIR) spectroscopy, whereas the particle size, zeta potential, and surface morphology were observed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release results revealed that more TOS and curcumin were released in the presence of GSH (5 mM) than the physiological pH value. Fluorescence microscopy images revealed that nanoformulated curcumin/rhodamine was uptaken by PAN02 pancreatic cancer cells. In vitro cytotoxicity assays showed higher cytotoxicity for nanoformulated TOS and/or curcumin than free TOS and/or curcumin. In addition, higher cytotoxicity was observed for combination drugs than free drugs alone. Most interestingly, at all tested concentrations of nanoformulated drugs (PAH-SS-PLGA, TOS, and curcumin), the calculated combination index (CI) value was less than one, which shows that TOS and curcumin have a synergistic effect on cellular proliferation inhibition. Overall, synthesized co-polymers are the best carriers for combination drugs, TOS, and curcumin, because they enhance the therapeutic efficacy and improve pancreatic cancer treatments.https://www.mdpi.com/1999-4923/12/8/778GSH-sensitive micellepoly(allylamine hydrochloride) (PAH)poly(lactic-co-glycolic acid) (PLGA)alpha-tocopheryl succinatecurcumin |
| spellingShingle | Tilahun Ayane Debele Hung-Chang Wu Shang-Rung Wu Yan-Shen Shan Wen-Pin Su Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer Pharmaceutics GSH-sensitive micelle poly(allylamine hydrochloride) (PAH) poly(lactic-co-glycolic acid) (PLGA) alpha-tocopheryl succinate curcumin |
| title | Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer |
| title_full | Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer |
| title_fullStr | Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer |
| title_full_unstemmed | Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer |
| title_short | Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer |
| title_sort | combination delivery of alpha tocopheryl succinate and curcumin using a gsh sensitive micelle pah ss plga to treat pancreatic cancer |
| topic | GSH-sensitive micelle poly(allylamine hydrochloride) (PAH) poly(lactic-co-glycolic acid) (PLGA) alpha-tocopheryl succinate curcumin |
| url | https://www.mdpi.com/1999-4923/12/8/778 |
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