Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles for Ovarian Cancer Therapyopen access
- Authors
- Jin, Chae Eun; Yoon, Moon Sup; Jo, Min Jeong; Kim, Seo Yeon; Lee, Jae Min; Kang, Su Jeong; Park, Chun-Woong; Kim, Jin-Seok; Shin, Dae Hwan
- Issue Date
- Apr-2023
- Publisher
- MDPI
- Keywords
- antitumor; combination therapy; micelle; mPEG-b-PCL; ovarian cancer; paclitaxel; pharmacokinetics; sorafenib
- Citation
- Pharmaceutics, v.15, no.4, pp 1 - 20
- Pages
- 20
- Journal Title
- Pharmaceutics
- Volume
- 15
- Number
- 4
- Start Page
- 1
- End Page
- 20
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/151889
- DOI
- 10.3390/pharmaceutics15041206
- ISSN
- 1999-4923
1999-4923
- Abstract
- 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-b-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). © 2023 by the authors.
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