Methods and Therapeutics Comprising Ligand-Targeted ELPs

Abstract

Disclosed herein are novel methods and compositions for targeting drug delivery systems to specific cells. One aspect relates to a drug delivery system comprising an elastin-like peptide (ELP) component and a ligand selected from the group consisting of mIgA and knob capable of either drug encapsulation or drug attachment. Further aspects relate to drug delivery systems comprising an elastin-like peptide (ELP) component and a ligand; wherein the ligand specifically binds to a receptor selected from the group consisting of CAR and pIgR. Further aspects include the novel transcytosing properties of the elastin-like peptide and the ligand, knob. Also provided are methods and pharmaceutical compositions comprising the disclosed therapeutics.

1 . A drug delivery agent comprising an elastin-like peptide (ELP) component and a ligand component, wherein:
 (a) the ligand component specifically binds to a CAR and/or pIgR receptor; and/or   (b) the ligand component is mIgA and/or knob ligand, or a biological equivalent thereof of the mIgA or knob ligand.   
     
     
         2 . The drug delivery agent of  claim 1 , further comprising a detectable label. 
     
     
         3 . The drug delivery agent of  claim 1 , further comprising a therapeutic agent. 
     
     
         4 . The drug delivery agent of  claim 3 , wherein the therapeutic agent is an anti-cancer drug. 
     
     
         5 . The drug delivery agent of  claim 1 , wherein the ELP component comprises a diblock. 
     
     
         6 . The drug delivery agent of  claim 5 , wherein the ELP component comprises a polypeptide with the sequence (VPGSG) 48 (VPGIG) 48  (SEQ ID NO: 12). 
     
     
         7 . The drug delivery agent of  claim 1 , wherein the ELP component comprises a polypeptide with the sequence (VPGSG) 96  (SEQ ID. NO: 13). 
     
     
         8 . The drug delivery agent of  claim 1 , wherein the ELP component comprises a polypeptide with the sequence (VPGIG) 96  (SEQ ID. NO: 14). 
     
     
         9 . The drug delivery agent of  claim 1 , wherein the ligand component is a mIgA ligand. 
     
     
         10 . The drug delivery agent of  claim 9 , wherein the mIgA ligand comprises a polypeptide having the sequence of SEQ ID. NO: 5 or a biological equivalent thereof. 
     
     
         11 . The drug delivery agent of  claim 1 , wherein the ligand component is a knob ligand. 
     
     
         12 . The drug delivery agent of  claim 11 , wherein the knob ligand comprises a polypeptide having the sequence of SEQ ID. NO: 4 or a biological equivalent thereof. 
     
     
         13 . A polynucleotide encoding the drug delivery agent of  claim 1 . 
     
     
         14 . A host cell comprising the polynucleotide of  claim 13 . 
     
     
         15 . A composition comprising a carrier and a drug delivery agent of  claim 1 . 
     
     
         16 . A method for preparing a drug delivery agent, comprising expressing the polynucleotide of  claim 13 . 
     
     
         17 . A method for preparing a drug delivery agent, comprising expressing the polynucleotide of in the host cell of  claim 14 . 
     
     
         18 . The method of  claim 16 , further comprising separating or purifying the drug delivery agent. 
     
     
         19 . A method for delivering a drug comprising an elastin-like peptide (ELP) to a cell, comprising contacting the cell with a drug delivery agent of  claim 1 , wherein:
 (a) the ligand component specifically binds to a CAR and/or pIgR receptor; and/or   (b) the ligand component is mIgA and/or knob ligand, or a biological equivalent thereof of the mIgA or knob ligand.   
     
     
         20 . A method for delivering a drug to the luminal area of LGACs by transcytosis, comprising contacting the LGAC with a drug delivery agent of  claim 1 , wherein:
 (a) the ligand component specifically binds to a CAR and/or pIgR receptor; and/or   (b) the ligand component is mIgA and/or knob ligand, or a biological equivalent thereof of the mIgA or knob ligand.   
     
     
         21 . The method of  claim 20 , wherein the drug is in contact with the ocular surface of the eye. 
     
     
         22 . The method of  claim 20 , wherein the drug is released from interstitial to luminal surfaces on a mucosal epithelial cell. 
     
     
         23 . The method of  claim 19 , wherein the contacting is in vitro or in vivo. 
     
     
         24 . The method of  claim 19 , wherein the cell is one or more of a mucosal cell, an epithelial cell or a hepatocyte and/or contained within a lacrimal gland or tissue. 
     
     
         25 . A method for treating a disease of the lacrimal gland, comprising administering to a patient in need of such treatment a drug delivery agent of  claim 1  wherein:
 (a) the ligand component specifically binds to a CAR and/or pIgR receptor; and/or 
 (b) the ligand component is mIgA and/or knob ligand, or a biological equivalent thereof of the mIgA or knob ligand, thereby treating the patient. 
 
     
     
         26 . The method of  claim 25 , wherein the disease is cancer or Sjorgren's Syndrome. 
     
     
         27 . The method of  claim 25 , wherein the administration is by inhalation or via injection.