Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
J Pharm Pharmacol. 2010 May;62(5):583-91. doi: 10.1211/jpp.62.05.0004.
The objective of this work was to explore the potential and safety of trimethyl chitosan (TMC) and PEGylated TMC for improved absorption of insulin after nasal administration.
The nasal absorption of insulin nanocomplexes of TMC or PEGylated TMC was evaluated in anaesthetized rats. Concomitantly, the histopathological effects of these nanocomplexes on rat nasal mucosa were studied using a perfusion fixation technique.
All insulin nanocomplexes containing TMC or PEGylated TMC showed a 34-47% reduction in the blood glucose concentration, when the insulin absorption through the rat nasal mucosa was measured indirectly. In addition, the relative pharmacodynamic bioavailability (F(dyn)) of the formulations was found to be dependent upon the charge ratio of insulin and polymer, regardless of polymer structure. The F(dyn) apparently decreased with increasing charge ratio of insulin : polymer. Although acute alterations in nasal morphology by the formulations were affected by the charge ratio of insulin and polymer, the formulation of insulin/PEGylated TMC nanocomplexes was shown to be less toxic to the nasal epithelial membrane than insulin/TMC nanocomplexes.
PEGylated TMC nanocomplexes were a suitable absorption enhancer for nasal delivery of insulin.
本研究旨在探讨三甲基壳聚糖（TMC）和聚乙二醇化 TMC 对提高胰岛素经鼻给药吸收的潜力和安全性。
在麻醉大鼠中评估了 TMC 或聚乙二醇化 TMC 胰岛素纳米复合物的鼻内吸收。同时，使用灌流固定技术研究了这些纳米复合物对大鼠鼻黏膜的组织病理学影响。
当通过大鼠鼻黏膜间接测量胰岛素吸收时，所有含 TMC 或聚乙二醇化 TMC 的胰岛素纳米复合物均使血糖浓度降低 34%-47%。此外，发现制剂的相对药效生物利用度（F(dyn)）取决于胰岛素和聚合物的电荷比，而与聚合物结构无关。F(dyn)显然随胰岛素与聚合物的电荷比增加而降低。尽管制剂对鼻形态的急性改变受胰岛素和聚合物的电荷比影响，但与胰岛素/TMC 纳米复合物相比，胰岛素/聚乙二醇化 TMC 纳米复合物对鼻上皮膜的毒性较小。
聚乙二醇化 TMC 纳米复合物是胰岛素经鼻给药的一种合适的吸收增强剂。
