Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer
Yu Been Shin,1,* Ju-Yeon Choi,2,* Dae Hwan Shin,1 Jeong-Won Lee2,3 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;...
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Dove Medical Press
2023-05-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/anticancer-evaluation-of-methoxy-polyethylene-glycol-b-polycaprolacton-peer-reviewed-fulltext-article-IJN |
| _version_ | 1797834951054327808 |
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| author | Shin YB Choi JY Shin DH Lee JW |
| author_facet | Shin YB Choi JY Shin DH Lee JW |
| author_sort | Shin YB |
| collection | DOAJ |
| description | Yu Been Shin,1,* Ju-Yeon Choi,2,* Dae Hwan Shin,1 Jeong-Won Lee2,3 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea*These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email dshin@chungbuk.ac.kr Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea, Tel +82-2-3410-1382, Fax +82-2-3410-0630, Email garden.lee@samsung.comPurpose: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied.Methods: Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy.Results: Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of − 0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation.Conclusion: There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.Keywords: ovarian cancer treatment, combination therapy, drug delivery, nanoformulation |
| first_indexed | 2024-04-09T14:45:43Z |
| format | Article |
| id | doaj.art-7eb7588927e04e488bb3d361dae08d40 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-09T14:45:43Z |
| publishDate | 2023-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-7eb7588927e04e488bb3d361dae08d402023-05-02T18:20:12ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-05-01Volume 182209222383406Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian CancerShin YBChoi JYShin DHLee JWYu Been Shin,1,* Ju-Yeon Choi,2,* Dae Hwan Shin,1 Jeong-Won Lee2,3 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea*These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email dshin@chungbuk.ac.kr Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea, Tel +82-2-3410-1382, Fax +82-2-3410-0630, Email garden.lee@samsung.comPurpose: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied.Methods: Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy.Results: Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of − 0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation.Conclusion: There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.Keywords: ovarian cancer treatment, combination therapy, drug delivery, nanoformulationhttps://www.dovepress.com/anticancer-evaluation-of-methoxy-polyethylene-glycol-b-polycaprolacton-peer-reviewed-fulltext-article-IJNovarian cancer treatmentcombination therapydrug deliverynanoformulation |
| spellingShingle | Shin YB Choi JY Shin DH Lee JW Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer International Journal of Nanomedicine ovarian cancer treatment combination therapy drug delivery nanoformulation |
| title | Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer |
| title_full | Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer |
| title_fullStr | Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer |
| title_full_unstemmed | Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer |
| title_short | Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer |
| title_sort | anticancer evaluation of methoxy poly ethylene glycol b poly caprolactone polymeric micelles encapsulating fenbendazole and rapamycin in ovarian cancer |
| topic | ovarian cancer treatment combination therapy drug delivery nanoformulation |
| url | https://www.dovepress.com/anticancer-evaluation-of-methoxy-polyethylene-glycol-b-polycaprolacton-peer-reviewed-fulltext-article-IJN |
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