Banga A K, Chien Y W
Controlled Drug-Delivery Research Center, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789.
Pharm Res. 1993 May;10(5):697-702. doi: 10.1023/a:1018955631835.
Hydrogels were synthesized as the drug reservoir matrix for peptide-based pharmaceuticals, and the iontophoretic release and transdermal delivery of three model peptides, insulin, calcitonin, and vasopressin, from these hydrogel-based iontotherapeutic devices were investigated. The swelling behavior of polyacrylamide-type hydrogel as a function of its monomer and cross-linker concentration was studied, and a hydrogel with minimal swelling was synthesized. The release of peptides from the hydrogel matrix was found to follow a Q vs t1/2 relationship under passive diffusion conditions, which shifted to a Q vs t relationship under iontophoresis-facilitated transport. The release flux (dQ/dt) of peptides was observed to decline when the electric current was turned off and was resumed when the current was turned on, thus allowing for modulation of drug release by varying the application parameters of iontophoresis-facilitated transport. The permeability coefficients for these peptides across the hairless rat skin were evaluated using the hydrogel formulations prepared from polyacrylamide, p-HEMA, and carbopol. A rank order of vasopressin > calcitonin > insulin was obtained in accordance with the order of molecular size.
水凝胶被合成为基于肽的药物的药物储库基质，并研究了三种模型肽，即胰岛素、降钙素和加压素，从这些基于水凝胶的离子治疗装置中的离子电渗释放和透皮递送。研究了聚丙烯酰胺型水凝胶的溶胀行为与其单体和交联剂浓度的关系，并合成了溶胀最小的水凝胶。发现在被动扩散条件下，肽从水凝胶基质中的释放遵循Q与t1/2的关系，而在离子电渗促进转运条件下，该关系转变为Q与t的关系。当关闭电流时，观察到肽的释放通量（dQ/dt）下降，而当电流开启时，释放通量恢复，因此可以通过改变离子电渗促进转运的应用参数来调节药物释放。使用由聚丙烯酰胺、聚甲基丙烯酸羟乙酯和卡波姆制备的水凝胶制剂评估了这些肽在无毛大鼠皮肤上的渗透系数。根据分子大小顺序，得到了加压素>降钙素>胰岛素的排序。
