Charge reversible polymers

Abstract

Described are charge reversible polymers, peptides and their resulting colloidal particles, comprising polymers and peptides having primary and secondary amines that are protected as easily hydrolysable amides. The amides are charge-reversible such that at neutral pH they are negatively charged but become positively charged at pH less than 6 and thus are relatively stable at neutral pH but quickly hydrolyze at pH below 6. Incorporating a drug in a micelle or a polymer comprised of the charge-reversible polymers or peptides provides a drug carrier for delivering the drug preferentially to the solid tumor or other targeted cells.

1 . A composition of matter comprising a compound having primary and secondary amines that are protected as easily hydrolysable amides. 
   
   
       2 . A composition of matter as defined in  claim 1 , wherein the compound is selected from the group consisting of polymers, peptides, and proteins. 
   
   
       3 . A composition of matter as defined in  claim 1 , wherein the amides are stable at neutral pH but hydrolyze at pH below 7. 
   
   
       4 . A composition of matter as defined in  claim 1 , wherein the compounds are charge-reversible such that at neutral pH they are negatively charged or neutral but become positively charged at pH less than 7. 
   
   
       5 . A composition of matter as defined in  claim 1 , further comprising a colloidal particle formed of the compound. 
   
   
       6 . A composition of matter as defined in  claim 1 , further comprising a micelle formed of the compound. 
   
   
       7 . A method of drug delivery to solid tumors and lysosomes, comprising forming of the compound of  claim 1  a carrier particle selected from the group consisting of a micelle and a colloidal particle, incorporating a drug in the carrier particle, and injecting the carrier particle into a subject having a solid tumor or lysosome. 
   
   
       8 . A method of drug delivery as defined in  claim 7 , wherein the drug is releasably bound to the compound. 
   
   
       9 . A composition, comprising a composition selected from the group consisting of peptides, proteins and other biopolymers that are negatively charged or neutral at pH higher than 7, but become positively charged at pH lower than 7. 
   
   
       10 . A composition as defined in  claim 9 , further comprising a bioactive agent and wherein the peptide, protein and other biopolymer hydrolyses at a delivery site of the bioactive agent to release the bioactive agent at the delivery site. 
   
   
       11 . A composition, comprising particles that are negatively charged or neutral at pH higher than 7, but become positively charged at pH lower than 7. 
   
   
       12 . A composition as defined in  claim 11 , further comprising a bioactive agent and wherein the bioactive agent is contained inside particles and wherein at least a portion of the particles hydrolyse at a delivery site of the bioactive agent to release the bioactive agent at the delivery site.