Synthesis and In Vivo Evaluation of Insulin-Loaded Whey Beads as an Oral Peptide Delivery System.
Synthesis and In Vivo Evaluation of Insulin-Loaded Whey Beads as an Oral Peptide Delivery System.
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胰岛素负载的乳头珠作为口服肽递送系统的合成和体内评估。
DOI：
10.3390/pharmaceutics13050656
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发表时间：
2021-05-04
期刊：
影响因子：
5.4
通讯作者：
Brayden DJ
中科院分区：
文献类型：
--
作者：
Heade J;McCartney F;Chenlo M;Marro OM;Severic M;Kent R;Bleiel SB;Alvarez CV;Griffin BT;Brayden DJ
对于许多糖尿病患者，需要每天终身注射胰岛素以有效地控制血糖水平和与疾病相关的并发症。这可能是一种负担，降低了患者的生活质量。我们的目标是开发一种更方便的口服给药系统，可能适用于胰岛素和其他肽。使用凝胶化将胰岛素包埋在由变性乳清蛋白分离物（dWPI）制成的1.5-mm珠粒中。然后将珠粒用气相二氧化硅Aerosil®空气干燥。包封率约为61%，胰岛素载量约为25 µg/mg。在模拟胃液和模拟肠液（SGF，SIF）中的溶出度显示，约50%的胰岛素从SGF中的珠粒中释放，然后在SIF中额外释放约10%。省略Aerosil®允许更大的胰岛素释放，表明其在珠表面上形成屏障。珠释放的胰岛素的圆二色性分析显示未改变的二级结构，并且胰岛素生物活性保留在转染的HepG 2细胞中以评估内源性胰岛素受体的活化。胰岛素包埋珠被发现提供对胰酶至少60分钟的部分保护。然后合成一个原型珠构建体，使用一个搅拌器系统和测试在体内使用大鼠肠道滴注生物测定。发现50 IU/kg的包封胰岛素在60分钟内使血糖水平降低55%，与皮下（s.c.）给药胰岛素（1 IU/kg）。滴注的胰岛素包埋珠粒产生的相对生物利用度为2.2%。总之，当优化时，基于dWPI的珠粒可能具有作为口服肽递送系统的潜力。
For many diabetics, daily, lifelong insulin injections are required to effectively manage blood glucose levels and the complications associated with the disease. This can be a burden and reduces patient quality of life. Our goal was to develop a more convenient oral delivery system that may be suitable for insulin and other peptides. Insulin was entrapped in 1.5-mm beads made from denatured whey protein isolate (dWPI) using gelation. Beads were then air-dried with fumed silica, Aerosil®. The encapsulation efficiency was ~61% and the insulin loading was ~25 µg/mg. Dissolution in simulated gastric-, and simulated intestinal fluids (SGF, SIF) showed that ~50% of the insulin was released from beads in SGF, followed by an additional ~10% release in SIF. The omission of Aerosil® allowed greater insulin release, suggesting that it formed a barrier on the bead surface. Circular dichroism analysis of bead-released insulin revealed an unaltered secondary structure, and insulin bioactivity was retained in HepG2 cells transfected to assess activation of the endogenous insulin receptors. Insulin-entrapped beads were found to provide partial protection against pancreatin for at least 60 min. A prototype bead construct was then synthesised using an encapsulator system and tested in vivo using a rat intestinal instillation bioassay. It was found that 50 IU/kg of entrapped insulin reduced plasma glucose levels by 55% in 60 min, similar to that induced by subcutaneously (s.c.)-administered insulin (1 IU/kg). The instilled insulin-entrapped beads produced a relative bioavailability of 2.2%. In conclusion, when optimised, dWPI-based beads may have potential as an oral peptide delivery system.
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影响因子：
3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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