Dendrimer drug conjugates for sustained intra-articular delivery

A conjugated dendrimer, represented by the following structural formula:

• or a pharmaceutically acceptable salt thereof
• wherein:
• D is a cationic dendrimer having end groups EG, wherein each EG includes an amine moiety,
• each L is a linker;
• each API is an active pharmaceutical ingredient;
• N is an integer power of 2 from 64 to 256;
• x, y, and z, each independently, is an integer from 1 to N;
• and
• wherein:
• (i) each CSG is a charge-shielding group having molecular weight of equal to or greater than 200 and less than 400 Da;
• and
• the ratio of (x+y+z)/N is from about 0.6 to about 0.9 or from about 0.4 to about 0.8;
• (ii) each CSG is a charge-shielding group having molecular weight of equal to or greater than 400 and less than 614 Da;
• and
• the ratio of (x+y+z)/N is from about 0.2 to about 0.6;
• (iii) each CSG is a charge-shielding group having molecular weight of equal to or greater than 614 and less than 820 Da;
• and
• the ratio of (x+y+z)/N is from about 0.15 to about 0.50;
• or
• (iv) each CSG is a charge-shielding group having molecular weight of equal to or greater than 820 and less than or equal to 1085 Da;
• and
• the ratio of (x+y+z)/N is from about 0.1 to about 0.4.