The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.
本发明提供了递送与内化肽连接的药剂的方法,在这种方法中,内化肽诱发的炎症反应可通过同时给药消炎药或通过将内化肽与
生物素或类似分子连接来抑制。这种方法的部分前提是实例中描述的结果,即高剂量给药与tat连接的药剂后会出现炎症反应,包括肥大细胞脱颗粒、
组胺释放和
组胺释放的典型后遗症,如发红、发热、肿胀和低血压。