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辣木叶标准化水提物负载水胶体薄膜敷贴剂:STZ/HFD 糖尿病大鼠模型中的体内皮肤安全性和伤口愈合评价。

Moringa oleifera standardised aqueous leaf extract-loaded hydrocolloid film dressing: in vivo dermal safety and wound healing evaluation in STZ/HFD diabetic rat model.

机构信息

Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.

Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.

出版信息

Drug Deliv Transl Res. 2019 Apr;9(2):453-468. doi: 10.1007/s13346-018-0510-z.

Abstract

Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.

摘要

先前,成功开发了负载辣木叶(MOL)标准水提物的薄膜,并在体外显示出潜在的伤口愈合活性。本研究的目的是评估这些 MOL 薄膜敷料(含有 0.1%、0.5%和 1% MOL)在糖尿病大鼠模型中的体内皮肤安全性和伤口愈合功效。在健康大鼠身上进行了急性皮肤毒性试验,观察了 14 天内的毒性迹象。对于伤口愈合研究,在 STZ/HFD 诱导的糖尿病大鼠模型上创建了切除和磨损伤口,并在 21 天内研究了伤口愈合情况。通过组织学染色、羟脯氨酸测定和 ELISA 测定评估伤口愈合相关生长因子、细胞因子和趋化因子。MOL 薄膜制剂未显示出皮肤毒性迹象。在切除伤口模型中,0.5%的薄膜在第 7 天使伤口闭合率显著提高了 77.67±7.28%,与对照组相比。而在磨损伤口中,0.5% MOL 薄膜使伤口闭合率在 81±4.5%时显著加快,与对照组相比。组织学发现和羟脯氨酸测定表明,用 0.5%和 1% MOL 薄膜处理的伤口观察到高胶原蛋白沉积和完全上皮化。所有 MOL 薄膜敷料均通过体内安全皮肤毒性测试证明无毒。结论是,负载 0.5% MOL 提取物的薄膜已被证明是加速 HFD/STZ 诱导的 II 型糖尿病模型上全厚度切除和部分厚度磨损伤口中糖尿病伤口愈合过程的最有前途的方法。

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