Encapsulation of hydrocortisone and mesalazine in zein microparticles.
Encapsulation of hydrocortisone and mesalazine in zein microparticles.
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DOI：
10.3390/pharmaceutics5020277
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发表时间：
2013-05-10
期刊：
影响因子：
5.4
通讯作者：
Steadman KJ
中科院分区：
文献类型：
--
作者：
Lau ET;Giddings SJ;Mohammed SG;Dubois P;Johnson SK;Stanley RA;Halley PJ;Steadman KJ
通过凝聚法将泼尼松龙载入玉米醇溶蛋白微粒中，对玉米醇溶蛋白作为一种口服药物递送系统进行了研究。为了研究该方法对其他药物的适用性，将氢化可的松（其结构与泼尼松龙相关）或美沙拉嗪（其结构不同，具有较小的分配系数LogP和可电离的官能团）载入玉米醇溶蛋白微粒。对玉米醇溶蛋白以及玉米醇溶蛋白微粒的体外消化率和电泳图谱进行了研究，以进一步深入了解将这种蛋白质用作药物递送系统的情况。氢化可的松载入玉米醇溶蛋白微粒的情况与所报道的泼尼松龙的情况相当，但美沙拉嗪的载入量变化很大。根据氢化可的松和玉米醇溶蛋白的起始量，相当于4毫克氢化可的松（临床使用剂量）的微粒平均量在60 - 115毫克之间，这对于口服给药是现实可行的。相比之下，递送250毫克美沙拉嗪（临床使用剂量）平均需要2.5克微粒，因此需要能够产生更高且更精确的美沙拉嗪载入量的替代包封方法。体外蛋白质消化率显示，与玉米醇溶蛋白原料相比，玉米醇溶蛋白微粒更耐消化，并且单个玉米醇溶蛋白肽不会优先凝聚到微粒中。综合来看，这些结果表明，有可能以使用更耐消化的玉米醇溶蛋白特定亚基作为起始材料制成的玉米醇溶蛋白微粒为基础，配制一种递送系统，将药物递送至下消化道。
Zein was investigated for use as an oral-drug delivery system by loading prednisolone into zein microparticles using coacervation. To investigate the adaptability of this method to other drugs, zein microparticles were loaded with hydrocortisone, which is structurally related to prednisolone; or mesalazine, which is structurally different having a smaller LogP and ionizable functional groups. Investigations into the in vitro digestibility, and the electrophoretic profile of zein, and zein microparticles were conducted to shed further insight on using this protein as a drug delivery system. Hydrocortisone loading into zein microparticles was comparable with that reported for prednisolone, but mesalazine loading was highly variable. Depending on the starting quantities of hydrocortisone and zein, the average amount of microparticles equivalent to 4 mg hydrocortisone, (a clinically used dose), ranged from 60–115 mg, which is realistic and practical for oral dosing. Comparatively, an average of 2.5 g of microparticles was required to deliver 250 mg of mesalazine (a clinically used dose), so alternate encapsulation methods that can produce higher and more precise mesalazine loading are required. In vitro protein digestibility revealed that zein microparticles were more resistant to digestion compared to the zein raw material, and that individual zein peptides are not preferentially coacervated into the microparticles. In combination, these results suggest that there is potential to formulate a delivery system based on zein microparticles made using specific subunits of zein that is more resistant to digestion as starting material, to deliver drugs to the lower gastrointestinal tract.