Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems
Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems
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DOI：
10.1007/s11095-017-2131-5
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发表时间：
2017-06-01
影响因子：
3.7
通讯作者：
Bernkop-Schnuerch, Andreas
中科院分区：
文献类型：
--
作者：
Hetenyi, Gergely;Griesser, Janine;Bernkop-Schnuerch, Andreas
该研究的目的是通过将两亲疏水改性、巯基化和预活化的聚合物（预活化硫聚合物）结合到自乳化药物递送系统（SEDDS）中来创建新型黏附药物递送系统。l -半胱氨酸甲酯共价连接到Pemulen TR-2的聚合主链上，并用2-巯基烟酸（2-MNA）预活化。这些硫代聚合物以0.3% （w/v）的浓度加入到SEDDS中。用动态光散射法测定了乳液的粒径分布和zeta电位。采用流变学测量、渗透研究和体外停留时间研究了经FDA（双醋酸荧光素）加标的硫硫聚合物- sedds在猪粘膜上的黏附性能。另外进行细胞活力测试。每克Pemulen TR-2聚合物可吸附734 +/- 58 μ mol l -半胱氨酸甲酯和562 +/- 71 μ mol 2-MNA。乳剂的液滴尺寸在180 ~ 270 nm之间。空白SEDDS的zeta电位值在-5.7 ~ -8.6 mV之间，而硫代聚合物-SEDDS的zeta电位值在-14.6 ~ -17.2 mV之间。含sedds -黏液的硫聚体和预活化硫聚体的黏性模量分别比对照提高了8倍和11倍。与空白SEDDS相比，硫柳汞-SEDDS中渗透黏液层的FDA量降低了2倍。硫柳汞- sedds的停留时间延长，超过45分钟。在细胞活力研究期间，未检测到严重的毒性作用。新开发的含硫代聚合物的SEDDS可能是一种很有前途的黏附口服给药工具。
The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS).L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed.734 +/- 58 mu mol L-Cysteine methyl ester and 562 +/- 71 mu mol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270 nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6 mV, whereas thiomers-SEDDS between -14.6 and -17.2 mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45 min. During cell viability studies no severe toxic effects were detected.The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.