Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities
Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves mus...
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/508 |
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| author | Aline Yen Ling Wang Kuan-Hung Chen Hsiu-Chao Lin Charles Yuen Yung Loh Yun-Ching Chang Ana Elena Aviña Chin-Ming Lee I-Ming Chu Fu-Chan Wei |
| author_facet | Aline Yen Ling Wang Kuan-Hung Chen Hsiu-Chao Lin Charles Yuen Yung Loh Yun-Ching Chang Ana Elena Aviña Chin-Ming Lee I-Ming Chu Fu-Chan Wei |
| author_sort | Aline Yen Ling Wang |
| collection | DOAJ |
| description | Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel–drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects. |
| first_indexed | 2024-03-11T08:17:21Z |
| format | Article |
| id | doaj.art-d3fc63abdec94224a492454fe1960f0b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:21Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d3fc63abdec94224a492454fe1960f0b2023-11-16T22:40:53ZengMDPI AGPharmaceutics1999-49232023-02-0115250810.3390/pharmaceutics15020508Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in ExtremitiesAline Yen Ling Wang0Kuan-Hung Chen1Hsiu-Chao Lin2Charles Yuen Yung Loh3Yun-Ching Chang4Ana Elena Aviña5Chin-Ming Lee6I-Ming Chu7Fu-Chan Wei8Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDepartment of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Plastic Surgery, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0SP, UKDepartment of Health Industry Technology Management, Chung Shan Medical University, Taichung 40201, TaiwanCenter for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanCenter for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanCenter for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanVascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel–drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects.https://www.mdpi.com/1999-4923/15/2/508mixed thermosensitive hydrogeltacrolimussustained releasenerve regenerationsciatic nerve |
| spellingShingle | Aline Yen Ling Wang Kuan-Hung Chen Hsiu-Chao Lin Charles Yuen Yung Loh Yun-Ching Chang Ana Elena Aviña Chin-Ming Lee I-Ming Chu Fu-Chan Wei Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities Pharmaceutics mixed thermosensitive hydrogel tacrolimus sustained release nerve regeneration sciatic nerve |
| title | Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities |
| title_full | Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities |
| title_fullStr | Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities |
| title_full_unstemmed | Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities |
| title_short | Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities |
| title_sort | sustained release of tacrolimus embedded in a mixed thermosensitive hydrogel for improving functional recovery of injured peripheral nerves in extremities |
| topic | mixed thermosensitive hydrogel tacrolimus sustained release nerve regeneration sciatic nerve |
| url | https://www.mdpi.com/1999-4923/15/2/508 |
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