Polyplexes
The present disclosure relates to compounds comprising (i) an active agent, wherein the active agent includes a charge at a predetermined pH, (ii) a polymer, wherein the polymer includes an opposite charge than the active agent at the predetermined pH; and (iii) a polyplex comprising the peptide and the polymer electrostatically bond together at the predetermined pH. In some embodiments, the active agent is a peptide, such as a peptide comprising MAPKAP kinase II inhibitory peptide, and in some embodiments the peptide includes a cell-penetrating peptide. In further embodiments, the disclosure provides methods for treating a disease or condition by administering a composition according to the present disclosure to a subject in need thereof.
1. A composition comprising:
A cationic peptide electrostatically bound to an anionic pH-responsive polymer comprising a poly((C 1 -C 6 )alkyl-acrylic acid) at a pH of between about 6.0 and about 8.0;
wherein the (C 1 -C 6 )alkyl group and the carboxylic acid group of the poly((C 1 -C 6 )alkyl-acrylic acid) are attached to the same carbon;
wherein the anionic pH-responsive polymer has a pKa of between 5.0 and about 7.4;
wherein the pH is above the pKa of the anionic pH-responsive polymer;
wherein the peptide is one or more sequences selected from SEQ. ID. NOS: 1-4; and
wherein the cationic active agent and the anionic pH-responsive polymer at least partially disassemble at a pH below about the pKa of the pH-responsive polymer.
2. The composition of claim 1 , wherein the cationic peptide electrostatically bound to the anionic pH-responsive polymer form a polyplex having a size of about 50 nm to about 500 nm.
3. A vascular graft, wherein the vascular graft comprises the composition of claim 1 .
4. A method of treating a vascular condition, comprising:
administering an effective amount of the composition of claim 1 to a subject in need thereof.
5. The method of claim 4 , wherein the vascular condition is intimal hyperplasia.
6. The method of claim 4 , wherein the step of administering comprises implanting a vascular graft that includes the composition of claim 1 in a subject in need thereof.