Sustained release of Apo A-I mimetic peptides and methods of treatment

摘要

A method including advancing a delivery device through a lumen of a blood vessel to a particular region in the blood vessel; and introducing a composition including a sustained-release carrier and an apolipoprotein A-I (apo A-I) synthetic mimetic peptide into a wall of the blood vessel at the particular region or a perivascular site, wherein the peptide has a property that renders the peptide effective in reverse cholesterol transport. A composition including an apolipoprotein A-I (apo A-I) synthetic peptide, or combination of an apo A-I synthetic mimetic peptide and an Acyl CoA cholesterol: acyltransferase (ACAT) inhibitor in a form suitable for delivery into a blood vessel, the peptide including an amino acid sequence in an order reverse to an order of various apo A-I mimetic peptides, or endogenous apo A-I analogs, or a chimera of helix 1 and helix 9 of endogenous apo A-I.

主权项

1. A composition, comprising: a first sustained-release carrier and a second sustained-release carrier, at least one of the first sustained-release carrier and the second sustained-release carrier comprising (1) a coating to facilitate targeting of the carrier and (2) a sustained release material comprising a cardiovascular targeting molecule comprising CRPPR (SEQ ID NO: 11) or a polyanhydride material comprising CPPP (SEQ ID NO: 12);
and a non-complexed apolipoprotein A-I (apo A-I) synthetic mimetic peptide and a non-complexed phospholipid, the non-complexed apo A-I synthetic mimetic peptide is encapsulated within the first sustained-release carrier and the non-complexed phospholipid is encapsulated within the second different sustained-release carrier such that upon sustained-release from the respective first and second sustained-release carriers, in situ complexing of the non-complexed apo A-I and non-complexed phospholipid occurs, and wherein the first sustained-release carrier and the second sustained release carrier are suspended within a hydrogel solution to form a dispersion, and the apo A-I synthetic mimetic peptide comprises an amino acid sequence including one of: (i) an 18-mer synthetic peptide comprising DWFKAFYDKVAEKFKEAF (SEQ ID NO: 1); and (ii) the reverse sequence of SEQ ID NO: 1.