Department of Pharmaceutical Sciences College of Pharmacy Nursing, & Allied Sciences, North Dakota State University, Dept.# 2665, Sudro Hall, Room 102A, PO Box 6050, Fargo, North Dakota, 58108-6050, USA.
Pharm Res. 2013 Mar;30(3):627-40. doi: 10.1007/s11095-012-0880-8. Epub 2012 Sep 14.
To develop poly 1,3-bis-(p-carboxyphenoxy) hexane-co-sebacic acid (p(CPH/SA)) microspheres for controlled basal insulin delivery and evaluate their in vivo efficacy and toxicity.
A series of CPH/SA copolymers with molar ratios 20/80, 40/60, and 50/50 were synthesized and characterized. The stability of encapsulated insulin and the fraction of insulin released from microspheres were assessed by different analytical techniques. The skin from the injection site of rats was examined microscopically for histomorphological changes.
Increasing the molar ratio of CPH/SA significantly (p < 0.05) improved insulin loading and controlled insulin release. However, dimer aggregates of insulin were observed as CPH/SA molar ratio increased. Co-encapsulation of zinc oxide with insulin inhibited dimer aggregate formation and further controlled insulin release. Insulin was stable after entrapment into microspheres and during in vitro release studies. Administration of microsphere formulations CPH/SA 40/60 and 50/50 with zinc oxide controlled insulin release and maintained basal insulin levels for 42 days in rats. Skin sections showed minimal inflammation with no evidence for histomorphological changes and toxicity.
Insulin-loaded CPH/SA microspheres demonstrated considerable potential as controlled delivery system for insulin. Copolymer microspheres maintained basal insulin levels for 42 days and were biodegradable and biocompatible.
开发聚 1,3-双-（对羧基苯氧基）己烷-co-癸二酸（p(CPH/SA)）微球用于控制基础胰岛素的输送，并评估其体内功效和毒性。
合成并表征了一系列摩尔比为 20/80、40/60 和 50/50 的 CPH/SA 共聚物。通过不同的分析技术评估了包封胰岛素的稳定性和微球中释放的胰岛素分数。检查大鼠注射部位皮肤的组织形态学变化。
CPH/SA 摩尔比的增加显著（p<0.05）提高了胰岛素的负载量并控制了胰岛素的释放。然而，随着 CPH/SA 摩尔比的增加，观察到了胰岛素的二聚体聚集。将氧化锌与胰岛素共包封可抑制二聚体聚集并进一步控制胰岛素释放。胰岛素在包封到微球中后和体外释放研究期间保持稳定。含有氧化锌的 CPH/SA 40/60 和 50/50 微球制剂的给药可控制胰岛素释放并在大鼠体内维持 42 天的基础胰岛素水平。皮肤切片显示出最小的炎症，没有组织形态学变化和毒性的证据。
载胰岛素的 CPH/SA 微球作为胰岛素的控制释放系统具有相当大的潜力。共聚物微球可维持 42 天的基础胰岛素水平，并且可生物降解和生物相容。
