Co-administration of an agent linked to an internalization peptide with an anti-inflammatory

摘要

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.

主权项

1. A method of delivering a pharmacological agent linked to an internalization peptide comprising RKKRRQRRR (SEQ ID NO:51) to a subject having or a risk of a disease treatable by the pharmacological agent, comprising
administering the pharmacological agent linked to the internalization peptide to the subject, and administering a mast cell degranulation inhibitor and/or an anti-histamine thereby reducing an inflammatory response due to mast cell degranulation induced by the internalization peptide, wherein the inflammatory response occurs within 60 minutes of administering the pharmacologic agent linked to the internalization peptide.