Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
Department of Neurosciences, Division: Neurology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
AAPS PharmSciTech. 2017 Oct;18(7):2479-2493. doi: 10.1208/s12249-017-0725-1. Epub 2017 Feb 15.
A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.
采用 TMC-PEGDMA-MAA 新型共聚微粒系统，合成了一种多功能平台，可递送达胰岛素、干扰素 β（INF-β）和红细胞生成素（EPO）这 3 种不同的蛋白质，作为一种智能 pH 响应型 2 倍胃和肠吸收系统。物理化学和物理力学研究证明了支持微粒系统控制蛋白质递释的结晶度程度。共聚体在进行体外和体内分析之前被制成片剂。在模拟胃液（SGF）中 2.5 小时后，与在模拟肠液（SIF）中相比，胰岛素的释放分数为 3.2%，其中胰岛素最大释放量为 83%。同样，INF-β和 EPO 在 SGF 中的释放量分别为 3%和 9.7%，在 SIF 中的最大释放量分别为 74%和 81.3%。体内研究表明，给药后 4 小时内血糖显著降低 54.19%，而对照制剂在相同时间内使血糖降低 74.6%。与皮下制剂的 0.9%峰值浓度相比，血清中 INF-β 的最大生物利用剂量计算为 1.3%，表明 24 小时内持续释放。与皮下对照制剂 8 小时后达到的 6.34%峰值浓度相比，载 EPO 的共聚物微粒的最大生物利用浓度为 1.6%。
