Monoterpenes-containing PEGylated transfersomes for enhancing joint cavity drug delivery evidenced by CLSM and double-sited microdialysis.
Monoterpenes-containing PEGylated transfersomes for enhancing joint cavity drug delivery evidenced by CLSM and double-sited microdialysis.
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DOI：
10.1016/j.msec.2020.110929
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Hang-sheng Zheng;Chang Xu;Ya-Rong Fei;Juan Wang;Mingshi Yang;Li Fang;Yinghui Wei;Chaofeng Mu;Yunjie Sheng;Fanzhu Li;Jiazhen Zhu;Chenghao Tao
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文献类型：
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作者：
Hang-sheng Zheng;Chang Xu;Ya-Rong Fei;Juan Wang;Mingshi Yang;Li Fang;Yinghui Wei;Chaofeng Mu;Yunjie Sheng;Fanzhu Li;Jiazhen Zhu;Chenghao Tao
滑膜组织是用于治疗类风湿性关节炎的药物递送的天然部位。我们前期的研究表明，混合单萜边缘活化的聚乙二醇化传递体（MMPTs）能显著促进抗炎药青藤碱（SIN）的透皮吸收。本研究的目的是研究MMPTs将SIN递送至关节腔中的滑膜组织的潜力。为此，使用常规脂质体（LPS）作为参照。采用透射电子显微镜、恒压挤出法和差示扫描量热法（DSC）对制剂进行理化表征。采用激光共聚焦扫描显微镜（CLSM）和双位点微透析-LC-MS/MS联用技术研究了MMPTs在不同皮肤层的分布及SIN在血液和关节腔中的药代动力学。结果表明，混合单萜能显著提高MMPTs的弹性，主要表现为主转变温度（Tm）和转变焓（△H）的降低。CLSM分析表明，MMPTs分布在皮肤深层，表明MMPTs可能通过皮肤转运SIN。相反，LPS被限制在角质层中，这阻止SIN穿透皮肤。双位点微透析药代动力学研究结果表明，MMPTs的SIN在关节腔内的稳态浓度（Css）和AUC 0 → t0分别是LPS的2.1倍和2.5倍。而在血液中，MMPTs的SIN的CsS和AUC 0 → t0约为LPS的1/3。本研究表明，MMPTs可以增强SIN向关节腔的递送。CLSM和双位点微透析技术的结合可以为药物的透皮和局部给药机制提供新的思路。
The synovial tissues are natural sites of drug delivery for the treatment of rheumatoid arthritis. Our previous study showed that mixed monoterpenes edge-activated PEGylated transfersomes (MMPTs) could significantly enhance the percutaneous absorption of sinomenine (SIN), an anti-inflammation drug. The aim of this study was to investigate the potential of MMPTs for delivery of SIN to the synovial tissues in joint cavities. To this end, conventional liposomes (LPSs) were used as a reference. Transmission electron microscope, constant pressure extrusion method, and differential scanning calorimetry (DSC) were used for physicochemical characterization of the formulations. Confocal laser scanning microscopy (CLSM) and double-sited microdialysis coupled with LC-MS/MS were exploited to study the distribution of MMPTs in different skin layers and pharmacokinetics of SIN in the blood and the joint cavities. The results showed that mixed monoterpenes could significantly enhance the elasticity of MMPTs, evidenced by a decrease in the main transition temperature (Tm) and transition enthalpy (△H). CLSM analyses demonstrated that MMPTs were distributed in deep layers of the skin, indicating that MMPTs might transport SIN through the skin. In contrast, LPSs were confined in the stratum corneum, which deterred SIN from penetrating through the skin. The results from double-sited microdialysis pharmacokinetics showed that in the joint cavities the steady state concentration (Css) and AUC0→tof SIN from MMPTs were 2.1-fold and 2.5-fold of those from LPSs, respectively. In contrast, in the blood the Cssand AUC0→tof SIN from MMPTs were about 1/3 of those from LPSs. This study suggested that MMPTs could enhance the delivery of SIN to the joint cavities. A combination of CLSM and double-sited microdialysis could give an insight into the mechanism of transdermal and local drug delivery.