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Bunge 总黄酮复合磷脂脂质体凝胶的制备、表征及深二度烧伤的药效学研究。

Preparation, characterization, and pharmacodynamic study on deep second degree burns of total flavonoids composite phospholipids liposome gel of Bunge.

机构信息

Department of Pharmacy, the 909th Hospital of PLA/the Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China.

Department of Pathology, the 909th Hospital of PLA/the Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China.

出版信息

Drug Dev Ind Pharm. 2020 Dec;46(12):2000-2009. doi: 10.1080/03639045.2020.1841787. Epub 2020 Nov 10.

Abstract

Wound healing is the treatment problem after deep second degree (II°) burns. The p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB/inhibitory factor-κB (NF-κB/IκB) signal pathways play significant role in angiogenesis and wound repair after burns.This study aimed to investigate the preparation, characterization and pharmacodynamics of the total flavonoids composite phospholipids liposome of Oxytropis falcata Bunge (TFOFB-CPL) on deep II° burns to research its biological activity and underlying mechanism. The TFOFB-CPL was prepared by thin-film dispersion method and the preparation process was optimized via central composite design. The TFOFB-CPL was then characterized by using particle size, polydispersity indexes (PDIs), zeta potential, encapsulation efficiency (EE) and morphology. Moerover, in vitro transdermal test and in vivo pharmacodynamic study included wound healing rate, hematoxylin-eosin (HE) staining, masson staning, western blotting and RT-PCR. The results showed that the therapeutic effects of TFOFB-CPL gel on deep II° burns, especially during wound healing were significant. TFOFB-CPL gel has a sustained-release effect during the treatment of deep II° burns with forming drug depot in the dermis layer. The wound healing rate of TFOFB-CPL gel group was near positive group and better than the other groups. TFOFB-CPL gel could promote the growth of epidermis, skin appendages, fibrovascular and collagen fibers, and had obvious anti-inflammatory effects. Moreover, TFOFB-CPL gel inhibited the activation of p38MAPK and the degradation of IκBα, and promoted the neonatal wounds during the early stage. Therefore, TFOFB-CPL gel could be considered as a novel preparation for treating deep II° burns.

摘要

创伤愈合是深度 II°烧伤后的治疗问题。p38 丝裂原活化蛋白激酶 (p38 MAPK) 和核因子-κB/抑制因子-κB (NF-κB/IκB) 信号通路在烧伤后血管生成和伤口修复中发挥重要作用。本研究旨在探讨黄花棘豆总黄酮复合磷脂脂质体(TFOFB-CPL)对深 II°烧伤的制备、表征和药效学,研究其生物学活性和作用机制。采用薄膜分散法制备 TFOFB-CPL,并通过中心复合设计优化制备工艺。采用粒径、多分散指数(PDI)、Zeta 电位、包封率(EE)和形态学对 TFOFB-CPL 进行表征。此外,还进行了体外透皮试验和体内药效学研究,包括创面愈合率、苏木精-伊红(HE)染色、Masson 染色、western blot 和 RT-PCR。结果表明,TFOFB-CPL 凝胶对深 II°烧伤,特别是在伤口愈合过程中有显著的治疗效果。TFOFB-CPL 凝胶在治疗深 II°烧伤时具有持续释放作用,在真皮层形成药物库。TFOFB-CPL 凝胶组的创面愈合率接近阳性组,优于其他组。TFOFB-CPL 凝胶能促进表皮、皮肤附属物、纤维血管和胶原纤维的生长,具有明显的抗炎作用。此外,TFOFB-CPL 凝胶抑制 p38MAPK 的激活和 IκBα的降解,促进早期新生儿创面的愈合。因此,TFOFB-CPL 凝胶可作为一种治疗深 II°烧伤的新型制剂。

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