Nano-fibular nanoparticle polymer-drug conjugate for sustained dermal delivery of retinoids

A conjugated polymer, comprising:

• a polymer;
• and
• an all-trans retinoid acid (ATRA) prodrug covalently bound to the polymer by a hydrolysable linker L,
• or a pharmaceutically acceptable salt thereof,
• wherein:
• the polymer comprises repeat units presented by structural formula (IA) or (II):
• and
• the ATRA prodrug is represented by structural formula (III):
• wherein:
• the hydrolysable linker L is a moiety selected from —C(O)O—, —OC(O)—, —NR*C(O)—, —C(O)NR*—, —(C═N—N(R*)2)—, —OC(O)NR*—, —NR*C(O)O—, —OC(O)NR*NR*—, and —O—, wherein R*, for each occurrence independently, is hydrogen or a C1-C4 alkyl;
• each R1, independently, is the ATRA prodrug, a halogen, nitro, —ORA, —SRA, —N(RA)2, —COORA, —OC(O)RA, —C(O)RA, —SO4RA, —PO4(RA)2, wherein RA is, for each occurrence independently, hydrogen, a C1-C6 alkyl, or a C6-C18 aryl, optionally substituted with one or more groups selected from —OH, —NH2, a C1-C3 (di)alkylamino, a halogen, —COOH, a C1-C4 alkoxy, and phenoxy;
• R2, R3, and R4, each independently, is a halogen, —OH, —SH, —NH2, —NO2, —COOH, —NHRB, —SO4H, —PO4H2, —PO4HRB, RB, —ORB, —SRB, —N(RB)2, —OORB, —OC(O)RB, —C(O)RB, —SO4RB, —PO4(RB)2, wherein RB is, for each occurrence independently, a C1-C6 alkyl or a C6-C18 aryl, optionally substituted with one or more groups selected from —OH, —NH2, a C1-C3 (di)alkylamino, a halogen, COOH, a C1-C4 alkoxy, and phenoxy;
• and
• each k, independently, is 1-6,
• wherein about 10% to about 50% of the R1 positions in the polymer are the ATRA prodrug.