Zwitterionic biocompatible polymers, methods, and uses thereof

A method comprising:

• (i) reacting a polyethyleneimine having a structure of
• with an α,β-unsaturated ester having a structure of
• to form an N-alkylated polyethyleneimine having a structure of
• wherein n is from 1 to 10,000 and R is H, —CH3, —(CH2)nCH3, —(CH2CH2O)nCH3, —(CH2CH2O)n(CH2)mCH3, —(CH2CH2O)n(CH2)mOH, —((CH2)nO)m((CH2)pO)q(CH2)rOH, —(CH2CH2O)nH, —(CH2)nOH, —(CH2)nO(CH2)mOH, —(CH2CH2OCH2CH2)nOH, —(CH2CH2O)nCH2CH2OH, —((CH2)1-8C(O)O)n(CH2)mOH, —((CH2)1-8C(O)O)n(CH2CH2O)m(OC(O)(CH2)1-8)pOH, —((CH2)1-8C(O)O)n(CH2CH2)m(OC(O)(CH2)1-8)pOH, —(CH2C(O)O)n(CH2CH2)m(OC(O)CH2)pOH, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))pOH, —((CH2)nOC(O)O)(CH2CH2)mOH, —(CH2)nNHC(O)(CH2)mOH, —(CH2)nC(O)NH(CH2)mOH, C1-n alkenyl, C1-n alkynyl, C6-10 aryl, pentafluorophenyl ester or succinimidyl;
• (ii) hydrolyzing the N-alkylated polyethyleneimine to provide a zwitterionic N-alkylated polyethyleneimine;
• and
• (iii) reacting the zwitterionic N-alkylated polyethyleneimine with a compound having a functional group capable of conjugating to a peptide, a protein, a monosaccharide, a disaccharide, an oligo/polysaccharide, a lipid, a nucleic acid, a polymer, a targeting ligand molecule, a prodrug, a small molecule drug, or any combination thereof to form a biocompatible zwitterionic polymer.

A biocompatible polymer, comprising a polymer backbone comprising

• one or more repeating units selected from a zwitterionic precursor repeating unit of Formula (I):
• and
• one or more repeating units selected from a zwitterionic repeating unit of Formula (II):
• wherein each R1 is independently —(CH2)n—, —(CH2)nO(CH2)m—, —(CH2CH2OCH2CH2)n—, —(CH2CH2O)nCH2CH2—, —(CH2CH2O)n(CH2)m—, —(CH2)n(CH2CH2O)m(CH2)p—, —((CH2)1-8C(O)O)n(CH2)m—, —((CH2)1-8C(O)O)n(CH2CH2O)m(OC(O)(CH2)1-8)p-, —((CH2)1-8C(O)O)n(CH2CH2)m(OC(O)(CH2)1-8)p-, —(CH2C(O)O)n(CH2CH2)m(OC(O)CH2)p—, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))p—, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))p—, —((CH2)nOC(O)O)(CH2CH2)m, —(CH2)nNHC(O)(CH2)m—, —(CH2)nC(O)NH(CH2)m, —(CH2)nS(O2)(CH2)m—, —(CH2)nS(O2)(CH2)mO(CH2)t—, —(CH2)nO—, —(CH2)nO(CH2)mO—, —(CH2CH2OCH2CH2)nO—, —(CH2CH2O)nCH2CH2O—, —(CH2CH2O)n(CH2)mO—, —(CH2)n(CH2CH2O)m(CH2)pO—, —((CH2)1-8C(O)O)n(CH2)mO—, —((CH2)1-8C(O)O)n(CH2CH2O)m(OC(O)(CH2)1-8)pO—, —((CH2)1-8C(O)O)n(CH2CH2)m(OC(O)(CH2)1-8)pO—, —(CH2C(O)O)n(CH2CH2)m(OC(O)CH2)pO—, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))pO—, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))pO—, —((CH2)nOC(O)O)(CH2CH2)mO—, —(CH2)nNHC(O)(CH2)mO—, —(CH2)nC(O)NH(CH2)mO—, —(CH2)nS(O2)(CH2)mO—, or —(CH2)nS(O2)(CH2)mO(CH2)tO—;
• each R2 is independently C, P(OR7), or S(═O);
• each R3 is independently O, NH, or OC(═O);
• each R4, R5 and R7 is independently H, —CH3, —(CH2)nCH3, —(CH2CH2O)nCH3, —(CH2CH2O)n(CH2)mCH3, —(CH2CH2O)n(CH2)mOH, —((CH2)nO)m((CH2)pO)q(CH2)rOH, —(CH2CH2O)nH, —(CH2)nOH, —(CH2)nO(CH2)mOH, —(CH2CH2OCH2CH2)nOH, —(CH2CH2O)nCH2CH2OH, —((CH2)1-8C(O)O)n(CH2)mOH, —((CH2)1-8C(O)O)n(CH2CH2O)m(OC(O)(CH2)1-8)pOH, —((CH2)1-8C(O)O)n(CH2CH2)m(OC(O)(CH2)1-8)pOH, —(CH2C(O)O)n(CH2CH2)m(OC(O)CH2)pOH, —(CH(CH3)C(O)O)n(CH2CH2)m(OC(O)CH(CH3))pOH, —((CH2)nOC(O)O)(CH2CH2)mOH, —(CH2)nNHC(O)(CH2)mOH, —(CH2)nC(O)NH(CH2)mOH, C1-n alkenyl, C1-n alkynyl, C6-10 aryl, pentafluorophenyl, or succinimidyl;
• R6 is F, Cl, Br, I, acetate, citrate, bicarbonate, carbonate, chlorate, dihydrogen phosphate, hydrogen phosphate, hydrogen sulfate, hydroxide, nitrate, nitride, nitrite, phosphate, sulfate, sulfide, sulfite, thiocyanate, thiosulfate, oxalate, perchlorate, chlorite, hypochlorite, periodate, iodate, hypoiodate, bromate, hypobromate, hypobromite, hydrogen carbonate, hydrogen sulfate, hydrogen sulfite, hydrogen oxalate, borate, tetraborate, hexfluorosilicate, tartrate, silicate, selenite, arsenate, ethanedioate, oxoethanoate, 2-hydroxyethanoate, propanoate, butanoate, pentanoate, butyrate, formate, lactate, maleate, oleate, oxalate, stearate, tartrate, urate, acrylate, glutamate, malonate, phthalate, barbiturate, cinnamate, hexanoate, folate, propionate, stearate, ascorbate, glutarate, azelate, benzilate, fumarate, gluconate, propiolate, tannate, gallate, titanate, trifluoroacetate, or diuranate;
• each n, m, p, q, and r is independently 1 to 10,000;
• and,
• t is 0 to 10,000.