In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery
Camptothecin (CPT) has been shown to exhibit anticancer activity against several cancers. Nevertheless, CPT is very hydrophobic with poor stability, and thus its medical application is limited. Therefore, various drug carriers have been exploited for effectively delivering CPT to the targeted cancer...
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MDPI AG
2023-05-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/15/11/2463 |
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| author | Yi-Cheng Huang Yang-Jie Zeng Yu-Wei Lin Hung-Chih Tai Trong-Ming Don |
| author_facet | Yi-Cheng Huang Yang-Jie Zeng Yu-Wei Lin Hung-Chih Tai Trong-Ming Don |
| author_sort | Yi-Cheng Huang |
| collection | DOAJ |
| description | Camptothecin (CPT) has been shown to exhibit anticancer activity against several cancers. Nevertheless, CPT is very hydrophobic with poor stability, and thus its medical application is limited. Therefore, various drug carriers have been exploited for effectively delivering CPT to the targeted cancer site. In this study, a dual pH/thermo-responsive block copolymer of poly(acrylic acid-<i>b</i>-<i>N</i>-isopropylacrylamide) (PAA-<i>b</i>-PNP) was synthesized and applied to encapsulate CPT. At temperatures above its cloud point, the block copolymer self-assembled to form nanoparticles (NPs) and in situ encapsulate CPT, owing to their hydrophobic interaction as evidenced by fluorescence spectrometry. Chitosan (CS) was further applied on the surface through the formation of a polyelectrolyte complex with PAA for improving biocompatibility. The average particle size and zeta potential of the developed PAA-<i>b</i>-PNP/CPT/CS NPs in a buffer solution were 168 nm and −30.6 mV, respectively. These NPs were still stable at least for 1 month. The PAA-<i>b</i>-PNP/CS NPs exhibited good biocompatibility toward NIH 3T3 cells. Moreover, they could protect the CPT at pH 2.0 with a very slow-release rate. At pH 6.0, these NPs could be internalized by Caco-2 cells, followed by intracellular release of the CPT. They became highly swollen at pH 7.4, and the released CPT was able to diffuse into the cells at higher intensity. Among several cancer cell lines, the highest cytotoxicity was observed for H460 cells. As a result, these environmentally-responsive NPs have the potential to be applied in oral administration. |
| first_indexed | 2024-03-11T02:58:20Z |
| format | Article |
| id | doaj.art-1e0a9931806e48808c608b696264ca86 |
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| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-11T02:58:20Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | Polymers |
| spelling | doaj.art-1e0a9931806e48808c608b696264ca862023-11-18T08:25:50ZengMDPI AGPolymers2073-43602023-05-011511246310.3390/polym15112463In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug DeliveryYi-Cheng Huang0Yang-Jie Zeng1Yu-Wei Lin2Hung-Chih Tai3Trong-Ming Don4Department of Food Science, National Taiwan Ocean University, No. 2, Beining Rd., Zhongzheng Dist., Keelung City 202301, TaiwanDepartment of Food Science, National Taiwan Ocean University, No. 2, Beining Rd., Zhongzheng Dist., Keelung City 202301, TaiwanDepartment of Chemical and Materials Engineering, Tamkang University, No. 151 Yingzhuan Rd., Tamsui Dist., New Taipei City 251301, TaiwanDepartment of Food Science, National Taiwan Ocean University, No. 2, Beining Rd., Zhongzheng Dist., Keelung City 202301, TaiwanDepartment of Chemical and Materials Engineering, Tamkang University, No. 151 Yingzhuan Rd., Tamsui Dist., New Taipei City 251301, TaiwanCamptothecin (CPT) has been shown to exhibit anticancer activity against several cancers. Nevertheless, CPT is very hydrophobic with poor stability, and thus its medical application is limited. Therefore, various drug carriers have been exploited for effectively delivering CPT to the targeted cancer site. In this study, a dual pH/thermo-responsive block copolymer of poly(acrylic acid-<i>b</i>-<i>N</i>-isopropylacrylamide) (PAA-<i>b</i>-PNP) was synthesized and applied to encapsulate CPT. At temperatures above its cloud point, the block copolymer self-assembled to form nanoparticles (NPs) and in situ encapsulate CPT, owing to their hydrophobic interaction as evidenced by fluorescence spectrometry. Chitosan (CS) was further applied on the surface through the formation of a polyelectrolyte complex with PAA for improving biocompatibility. The average particle size and zeta potential of the developed PAA-<i>b</i>-PNP/CPT/CS NPs in a buffer solution were 168 nm and −30.6 mV, respectively. These NPs were still stable at least for 1 month. The PAA-<i>b</i>-PNP/CS NPs exhibited good biocompatibility toward NIH 3T3 cells. Moreover, they could protect the CPT at pH 2.0 with a very slow-release rate. At pH 6.0, these NPs could be internalized by Caco-2 cells, followed by intracellular release of the CPT. They became highly swollen at pH 7.4, and the released CPT was able to diffuse into the cells at higher intensity. Among several cancer cell lines, the highest cytotoxicity was observed for H460 cells. As a result, these environmentally-responsive NPs have the potential to be applied in oral administration.https://www.mdpi.com/2073-4360/15/11/2463stimuli-responsive polymerspoly(acrylic acid)poly(<i>N</i>-isopropylacrylamide)chitosancamptothecindrug delivery |
| spellingShingle | Yi-Cheng Huang Yang-Jie Zeng Yu-Wei Lin Hung-Chih Tai Trong-Ming Don In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery Polymers stimuli-responsive polymers poly(acrylic acid) poly(<i>N</i>-isopropylacrylamide) chitosan camptothecin drug delivery |
| title | In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery |
| title_full | In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery |
| title_fullStr | In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery |
| title_full_unstemmed | In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery |
| title_short | In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-<i>b</i>-Poly(<i>N</i>-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery |
| title_sort | in situ encapsulation of camptothecin by self assembly of poly acrylic acid i b i poly i n i isopropylacrylamide and chitosan for controlled drug delivery |
| topic | stimuli-responsive polymers poly(acrylic acid) poly(<i>N</i>-isopropylacrylamide) chitosan camptothecin drug delivery |
| url | https://www.mdpi.com/2073-4360/15/11/2463 |
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