Development of triptolide-nanoemulsion gels for percutaneous administration: physicochemical, transport, pharmacokinetic and pharmacodynamic characteristics.
Development of triptolide-nanoemulsion gels for percutaneous administration: physicochemical, transport, pharmacokinetic and pharmacodynamic characteristics.
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DOI：
10.1186/s12951-017-0323-0
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发表时间：
2017-12-04
影响因子：
10.2
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Yang M;Gu Y;Yang D;Tang X;Liu J
这项工作的目的是提供有用的信息，使用纳米乳剂的雷公藤甲素经皮给药。脂质纳米系统在透皮给药方面具有巨大的潜力。制备纳米乳和纳米乳凝胶以增强经皮渗透。比较雷公藤甲素纳米乳和纳米乳凝胶的微观结构和体内外经皮给药特性。同时考察了纳米乳和纳米乳凝胶经皮给药过程中的完整性及其对皮肤表面的影响。采用差示扫描量热法（DSC）和傅里叶变换红外光谱法（FTIR）研究了纳米乳液和纳米乳液凝胶的渗透机理。使用激光扫描共聚焦显微镜探测荧光标记的纳米乳液的传输特性。还研究了小鼠耳中的慢性皮炎/湿疹模型和TPL-纳米乳凝胶的药效学。与TPL凝胶相比，显著更大的累积量的TPL-纳米乳液凝胶和TPL-纳米乳液在体外穿透大鼠皮肤。体内微透析显示TPL-NPs的浓度-时间曲线AUC 0-t大于TPL-凝胶。同时，TPL-NPs对皮肤表面有较大的影响。通过水合角蛋白并改变角质层脂质和角蛋白的结构，纳米乳剂和纳米乳剂凝胶影响皮肤以促进经皮药物渗透。毛囊和角质层在这种透皮给药系统中也很重要。中、高剂量的纳米乳凝胶剂能显著改善小鼠耳皮炎湿疹炎症和水肿的症状，并能降低IFN-γ和IL-4的表达。雷公藤多苷纳米乳凝胶剂对胃肠道的损伤较雷公藤口服片轻。纳米乳可用于药物的经皮稳定释放和维持有效药物浓度。与其他载体相比，TPL-纳米乳凝胶提供了更高的经皮量。这些结果表明，纳米乳凝胶可能是有前途的经皮载体的TPL。该纳米乳凝胶对小鼠皮炎/湿疹模型具有显著的治疗效果，有望为临床治疗皮炎/湿疹的透皮给药系统提供一种新的、低毒的、长效的制剂。本文的在线版本（10.1186/s12951-017-0323-0）包含补充材料，可供授权用户使用。
This work aimed to provide useful information on the use of nanoemulsions for the percutaneous administration of triptolide. Lipid nanosystems have great potential for transdermal drug delivery. Nanoemulsions and nanoemulsion gels were prepared to enhance percutaneous permeation. Microstructure and in vitro/in vivo percutaneous delivery characteristics of triptolide (TPL)-nanoemulsions and TPL-nanoemulsion gels were compared. The integrity of the nanoemulsions and nanoemulsion gels during transdermal delivery and its effects on the surface of skin were also investigated. The penetration mechanisms of nanoemulsions and nanoemulsion gels were investigated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The transport characteristics of fluorescence-labelled nanoemulsions were probed using laser scanning confocal microscopy. A chronic dermatitis/eczema model in mice ears and the pharmacodynamic of the TPL-nanoemulsion gels were also investigated. Compared to TPL gels, significantly greater cumulative amounts of TPL-nanoemulsion gels and TPL-nanoemulsions penetrated rat skin in vitro. The in vivo microdialysis showed the concentration–time curve AUC0–t for TPL-NPs is bigger than the TPL-gels. At the same time, TPL-NPs had a larger effect on the surface of skin. By hydrating keratin and changing the structure of both the stratum corneum lipids and keratin, nanoemulsions and nanoemulsion gels influence skin to promote percutaneous drug penetration. Both hairfollicles and the stratum corneum are also important in this transdermal drug delivery system. Moderate and high dosages of the TPL-nanoemulsion gels can significantly improve the symptoms of dermatitis/eczema inflammation and edema erythematic in mice ears and can reduce the expression of IFN-γ and IL-4. Moreover, the TPL-nanoemulsion gels cause less gastrointestinal damage than that of the Tripterygium wilfordii oral tablet does. Nanoemulsions could be suitable for transdermal stably releasing drugs and maintaining the effective drug concentration. The TPL-nanoemulsion gels provided higher percutaneous amounts than other carriers did. These findings suggest that nanoemulsion gels could be promising percutaneous carriers for TPL. The TPL-nanoemulsion gels have a significant treatment effect on dermatitis/eczema in the mice model and is expected to provide a new, low-toxicity and long-term preparation for the clinical treatment of dermatitis/eczema in transdermal drug delivery systems. The online version of this article (10.1186/s12951-017-0323-0) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Malipeddi, Venkata Ramana;Awasthi, Rajendra;Dua, Kamal
通讯作者：
Dua, Kamal
影响因子：
3.4
作者：
Calderilla-Fajardo, SB;Cázares-Delgadillo, J;Robles, R
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Robles, R
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6
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Hussain, Afzal;Samad, Abdus;Ahmed, F. J.
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作者：
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通讯作者：
Sharma, Prashant K.
影响因子：
5.8
作者：
Alves, Marta P.;Scarrone, Ana L.;Guterres, Silvia S.
通讯作者：
Guterres, Silvia S.