A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy
Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The cop...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/8/413 |
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| author | Hsiu-Chao Lin Madonna Rica Anggelia Chih-Chi Cheng Kuan-Lin Ku Hui-Yun Cheng Chih-Jen Wen Aline Yen Ling Wang Cheng-Hung Lin I-Ming Chu |
| author_facet | Hsiu-Chao Lin Madonna Rica Anggelia Chih-Chi Cheng Kuan-Lin Ku Hui-Yun Cheng Chih-Jen Wen Aline Yen Ling Wang Cheng-Hung Lin I-Ming Chu |
| author_sort | Hsiu-Chao Lin |
| collection | DOAJ |
| description | Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(<span style="font-variant: small-caps;">l</span>-alanine) with <span style="font-variant: small-caps;">l</span>-lysine segments at both ends (P−Lys−Ala−PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy. |
| first_indexed | 2024-04-11T13:46:26Z |
| format | Article |
| id | doaj.art-a45dd1f5b61148a6a5d5a7e35fe51fd4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:46:26Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a45dd1f5b61148a6a5d5a7e35fe51fd42022-12-22T04:21:03ZengMDPI AGPharmaceutics1999-49232019-08-0111841310.3390/pharmaceutics11080413pharmaceutics11080413A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive TherapyHsiu-Chao Lin0Madonna Rica Anggelia1Chih-Chi Cheng2Kuan-Lin Ku3Hui-Yun Cheng4Chih-Jen Wen5Aline Yen Ling Wang6Cheng-Hung Lin7I-Ming Chu8Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, TaiwanCenter for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, TaiwanDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu 300, TaiwanDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu 300, TaiwanCenter for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, TaiwanCenter for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, TaiwanCenter for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, TaiwanCenter for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, TaiwanDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu 300, TaiwanTacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(<span style="font-variant: small-caps;">l</span>-alanine) with <span style="font-variant: small-caps;">l</span>-lysine segments at both ends (P−Lys−Ala−PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy.https://www.mdpi.com/1999-4923/11/8/413allotransplantationhydrogelssustained deliverytacrolimus |
| spellingShingle | Hsiu-Chao Lin Madonna Rica Anggelia Chih-Chi Cheng Kuan-Lin Ku Hui-Yun Cheng Chih-Jen Wen Aline Yen Ling Wang Cheng-Hung Lin I-Ming Chu A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy Pharmaceutics allotransplantation hydrogels sustained delivery tacrolimus |
| title | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
| title_full | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
| title_fullStr | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
| title_full_unstemmed | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
| title_short | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
| title_sort | mixed thermosensitive hydrogel system for sustained delivery of tacrolimus for immunosuppressive therapy |
| topic | allotransplantation hydrogels sustained delivery tacrolimus |
| url | https://www.mdpi.com/1999-4923/11/8/413 |
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