Novel approach for enhancing skin allograft survival by bioadhesive nanoparticles loaded with rapamycin.

Autor: Liu Y; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Ouyang Y; Department of School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China., Yu L; Department of School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China., Wang P; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Peng Z; Department of School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China., Liu H; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Zhao S; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Wang H; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Zhou Z; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China., Deng Y; Department of School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China. Electronic address: dengy67@mail.sysu.edu.cn., Liu Y; Department of School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China; Department of School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, No.66, Gongchang Road, Shenzhen, 518107, China. Electronic address: liuyang65@mail.sysu.edu.cn., Xie J; Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China. Electronic address: xiejulin@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Feb 15; Vol. 651, pp. 123742. Date of Electronic Publication: 2023 Dec 25.
DOI: 10.1016/j.ijpharm.2023.123742
Abstrakt: Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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