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An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.
Li, Zhanrong; Liu, Ruixing; Zhang, Xiacong; Guo, Zhihua; Geng, Xingchen; Chu, Dandan; Cui, Haohao; Zhang, Afang; Li, Wen; Zhu, Lei; Li, Jingguo.
Afiliación
  • Li Z; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Liu R; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Zhang X; International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China.
  • Guo Z; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Geng X; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Chu D; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Cui H; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
  • Zhang A; International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China.
  • Li W; International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China. Electronic address: wli@shu.edu.cn.
  • Zhu L; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China. Electronic address: hnyks135@126.com.
  • Li J; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China. Electronic address: lijingguo@zzu.edu.cn.
J Control Release ; 369: 604-616, 2024 May.
Article en En | MEDLINE | ID: mdl-38582337
ABSTRACT
Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Córnea / Hidrogeles / Triterpenos Pentacíclicos Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Córnea / Hidrogeles / Triterpenos Pentacíclicos Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos