CPC A61K 31/713 (2013.01) [A61K 9/1075 (2013.01); A61K 47/549 (2017.08); A61K 47/58 (2017.08); A61K 47/60 (2017.08); A61K 47/6907 (2017.08); A61K 48/0041 (2013.01); C08F 290/062 (2013.01); C08F 293/005 (2013.01); C12N 15/111 (2013.01); C12N 15/87 (2013.01); C12N 2320/32 (2013.01); Y02A 50/30 (2018.01)] | 16 Claims |
1. A micelle-like assembly, wherein the micelle-like assembly comprises a plurality of block copolymers of Formula I:
wherein
A0, A1, A2, A3 and A4 are independently selected from the group consisting of —C—, —C—C—, —C(O)(C)aC(O)O—, —O(C)aC(O)—, and —O(C)bO—; wherein,
a is 1-4;
b is 2-4;
Y4 is selected from the group consisting of hydrogen, -(1C-10C)alkyl,-(3C-6C)cycloalkyl, —O—(1C-10C)alkyl, —C(O)O(1C-10C)alkyl, -(4C-10C)heteroaryl, and -(6C-10C)aryl, any of which is optionally substituted with one or more fluorine groups;
Y0, Y1, and Y2 are independently selected from the group consisting of a covalent bond, -(1C-10C)alkyl-, —C(O)O(2C-10C) alkyl-, —OC(O)(1C-10C) alkyl-, —O(2C-10C)alkyl-, —S(2C-10C)alkyl-, —C(O)NR6(2C-10C) alkyl-, -(4C-10C)heteroaryl-, and -(6C-10C)aryl-;
Y3 is selected from the group consisting of a covalent bond, -(1C-10C)alkyl-, -(4C-10C)heteroaryl-, and -(6C-10C)aryl-;
wherein tetravalent carbon atoms of A0-A4 that are not fully substituted with R1-R5 and Y0-Y4 are completed with an appropriate number of hydrogen atoms;
R1, R2, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, —CN, alkyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more fluorine atoms;
Q0 is a residue selected from the group consisting of residues which are hydrophilic at physiologic pH; conjugatable or functionalizable residues; and hydrogen;
Q1 is a residue which is hydrophilic at physiological pH;
Q2 is a residue which is positively charged at physiological pH;
Q3 is a residue which is negatively charged at physiological pH, but undergoes protonation at lower pH;
m is a mole fraction of about 0 to less than 1.0;
n is a mole fraction of greater than 0 to about 1.0; wherein m+n=1;
p is a mole fraction of 0.1 to 0.9;
q is a mole fraction of 0.1 to 0.9;
r is present up to a mole fraction of 0.8; wherein p+q+r=1;
v is from about 1 to about 25 kDa; and
w is from about 1 to about 50 kDa.
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