Composition and Method for Therapeutic Agent Delivery During Pregnancy

Abstract

A composition including an elastin-like polypeptide (ELP) coupled to a therapeutic agent is provided. The ELP comprises at least about 5 repeats of the amino acid sequence VPGXG. Further provided is a method of using the composition for therapeutic agent delivery during pregnancy to reduce the amount of the therapeutic agent crossing a placenta in a pregnant subject. The method includes administering to the pregnant subject an effective amount of the composition comprising the ELP coupled to the therapeutic agent.

1 . A method of delivering a therapeutic agent to a pregnant subject in need thereof, comprising:
 administering to the pregnant subject an effective amount of a composition comprising an elastin-like polypeptide (ELP) coupled to the therapeutic agent that is contraindicated for fetal development,   wherein the ELP includes an amino acid sequence having at least about 5 repeats of the amino acid sequence VPGXG (SEQ ID NO: 1), where X is any amino acid except proline.   
     
     
         2 . The method of  claim 1 , wherein the therapeutic agent is VEGF. 
     
     
         3 . The method of  claim 2 , wherein the composition comprises the amino acid sequence of SEQ ID NOs: 14. 
     
     
         4 . The method of  claim 1 , wherein the therapeutic agent is a peptide-selected from the group consisting of an NF-κB inhibitory peptide and an NADPH oxidase inhibitory peptide. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic agent is a Pregnancy Category X drug. 
     
     
         6 . The method of  claim 1 , wherein the therapeutic agent is a Pregnancy Category B, C, or D drug. 
     
     
         7 . The method of  claim 1 , wherein the therapeutic agent is selected from the group set forth in Table 1. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic agent is regarded as harmful to fetal development. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic agent is prevented from entering the fetal circulation. 
     
     
         10 . The method of  claim 1 , and further comprising confirming that the therapeutic agent has not entered fetal circulation. 
     
     
         11 . The method of  claim 1 , wherein the composition further comprises a cell-penetrating peptide, an organ targeting peptide, or both coupled to the ELP. 
     
     
         12 . A method of making a composition for treating a pregnant subject with a therapeutic agent while reducing or preventing the therapeutic agent from entering the fetal circulation, comprising: selecting the therapeutic agent; and coupling an elastin-like polypeptide (ELP) to the a therapeutic agent, wherein the ELP includes an amino acid sequence having at least about 5 repeats of the amino acid sequence VPGXG (SEQ ID NO: 1), where X is any amino acid except proline. 
     
     
         13 . The method of  claim 12 , wherein the therapeutic agent is VEGF. 
     
     
         14 . The method of  claim 13 , wherein the composition comprises the amino acid sequence of SEQ ID NOs: 14. 
     
     
         15 . The method of  claim 12 , wherein the therapeutic agent is a peptide-selected from the group consisting of an NF-κB inhibitory peptide and an NADPH oxidase inhibitory peptide. 
     
     
         16 . The method of  claim 12 , wherein the therapeutic agent is regarded as harmful to fetal development. 
     
     
         17 . The method of  claim 12 , wherein the therapeutic agent is a Pregnancy Category X drug. 
     
     
         18 . The method of  claim 12 , wherein the therapeutic agent is a Pregnancy Category B, C, or D drug. 
     
     
         19 . The method of  claim 12 , wherein the therapeutic agent is selected from the group set forth in Table 1. 
     
     
         20 . The method of  claim 12 , wherein the composition further comprises a cell-penetrating peptide, an organ targeting peptide, or both coupled to the ELP. 
     
     
         21 . A composition, comprising an elastin-like polypeptide coupled to a therapeutic agent, the therapeutic agent selected from the group consisting of VEGF, an NF-κB inhibitory peptide, and an NADPH oxidase inhibitory peptide. 
     
     
         22 . The composition of  claim 21 , wherein the composition further comprises a cell-penetrating peptide, an organ targeting peptide, or both coupled to the ELP.