Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy
Ovarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1206 |
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| author | Chae Eun Jin Moon Sup Yoon Min Jeong Jo Seo Yeon Kim Jae Min Lee Su Jeong Kang Chun-Woong Park Jin-Seok Kim Dae Hwan Shin |
| author_facet | Chae Eun Jin Moon Sup Yoon Min Jeong Jo Seo Yeon Kim Jae Min Lee Su Jeong Kang Chun-Woong Park Jin-Seok Kim Dae Hwan Shin |
| author_sort | Chae Eun Jin |
| collection | DOAJ |
| description | Ovarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF) with various polymers were prepared, and the optimal polymer (mPEG-<i>b</i>-PCL) was selected by measuring drug loading (%), encapsulation efficiency (%), particle size, polydispersity index, and zeta potential. The final formulation was selected based on a molar ratio (PTX:SRF = 1:2.3) with synergistic effects on two ovarian cancer cell lines (SKOV3-red-fluc, HeyA8). In the in vitro release assay, PTX/SRF micelles showed a slower release than PTX and SRF single micelles. In pharmacokinetic evaluation, PTX/SRF micelles showed improved bioavailability compared to PTX/SRF solution. In in vivo toxicity assays, no significant differences were observed in body weight between the micellar formulation and the control group. The anticancer effect of PTX/SRF combination therapy was improved compared to the use of a single drug. In the xenografted BALB/c mouse model, the tumor growth inhibition rate of PTX/SRF micelles was 90.44%. Accordingly, PTX/SRF micelles showed improved anticancer effects compared to single-drug therapy in ovarian cancer (SKOV3-red-fluc). |
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| issn | 1999-4923 |
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| last_indexed | 2024-03-11T04:38:18Z |
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| series | Pharmaceutics |
| spelling | doaj.art-7bd7f8ee609947a2b2efe76e5c27c39a2023-11-17T20:54:14ZengMDPI AGPharmaceutics1999-49232023-04-01154120610.3390/pharmaceutics15041206Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer TherapyChae Eun Jin0Moon Sup Yoon1Min Jeong Jo2Seo Yeon Kim3Jae Min Lee4Su Jeong Kang5Chun-Woong Park6Jin-Seok Kim7Dae Hwan Shin8College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaDrug Information Research Institute (DIRI), College of Pharmacy, Sookmyung Women’s University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of KoreaOvarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF) with various polymers were prepared, and the optimal polymer (mPEG-<i>b</i>-PCL) was selected by measuring drug loading (%), encapsulation efficiency (%), particle size, polydispersity index, and zeta potential. The final formulation was selected based on a molar ratio (PTX:SRF = 1:2.3) with synergistic effects on two ovarian cancer cell lines (SKOV3-red-fluc, HeyA8). In the in vitro release assay, PTX/SRF micelles showed a slower release than PTX and SRF single micelles. In pharmacokinetic evaluation, PTX/SRF micelles showed improved bioavailability compared to PTX/SRF solution. In in vivo toxicity assays, no significant differences were observed in body weight between the micellar formulation and the control group. The anticancer effect of PTX/SRF combination therapy was improved compared to the use of a single drug. In the xenografted BALB/c mouse model, the tumor growth inhibition rate of PTX/SRF micelles was 90.44%. Accordingly, PTX/SRF micelles showed improved anticancer effects compared to single-drug therapy in ovarian cancer (SKOV3-red-fluc).https://www.mdpi.com/1999-4923/15/4/1206ovarian cancerpaclitaxelsorafenibcombination therapymPEG-<i>b</i>-PCLmicelle |
| spellingShingle | Chae Eun Jin Moon Sup Yoon Min Jeong Jo Seo Yeon Kim Jae Min Lee Su Jeong Kang Chun-Woong Park Jin-Seok Kim Dae Hwan Shin Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy Pharmaceutics ovarian cancer paclitaxel sorafenib combination therapy mPEG-<i>b</i>-PCL micelle |
| title | Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy |
| title_full | Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy |
| title_fullStr | Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy |
| title_full_unstemmed | Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy |
| title_short | Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-<i>b</i>-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapy |
| title_sort | synergistic encapsulation of paclitaxel and sorafenib by methoxy poly ethylene glycol i b i poly caprolactone polymeric micelles for ovarian cancer therapy |
| topic | ovarian cancer paclitaxel sorafenib combination therapy mPEG-<i>b</i>-PCL micelle |
| url | https://www.mdpi.com/1999-4923/15/4/1206 |
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