Cyclodextrin grafted biocompatible amphilphilic polymer and methods of preparation and use thereof

A cyclodextrin grafted biocompatible polymer having the formula 2

• 5
• wherein R′ is H or a targeting moiety;
• X is a linker having the formula
• -Q-Z-Q′-
• wherein Q is covalently bonded to the hydrophilic polymer chain either directly or by means of a pendant alkyl or other functional group and Q′ is covalently bonded to the cylodextrin at the 2, 3 or 6 position thereby replacing either OR1, OR2 or OR3 group respectively;
• Q and Q′ are independently members selected from the group consisting of NR4, S, O, CO, CONH, and COO;
• Z is a member selected from the group consisting of an alkylene disulfide, [—(CH2)aS—S(CH2)a—], alkylene [—(CH2)a—], alkylene oxide (—[(CH2)aO]b(CH2)a—), or a short chained peptide where a is an integer of 1 to 10 and b is an integer of 1 to 20;
• R1, R2, R3 and R4 are independently members selected from the group consisting of H, alkyl (Cn′H2n′+1), alkenyl (Cn′+1H2(n′+1)−1) or acyl (Cn′H2n′+1CO) where n′ is an integer of 1 to 16;
• q is an integer of 5, 6 or 7;
• w is an integer such as to provide between 2 and 15 cyclodextrin units per 20 KD PEG backbone chain, and m and n are integers sufficient that when combined with w they represent a polyethylene oxide polymeric chain having the molecular weight of 5,000 to 70,000 with the proviso that monomeric units on the biocompatible polymer backbone containing the grafted cyclodextrin units represented by w do not have to be consecutively joined but may be randomly or uniformly distributed along polymer backbone.

A cyclodextrin grafted biocompatible polymer having the formula 3

• 6
• wherein R′ is H or a targeting moiety;
• Q is covalently bonded to the hydrophilic polymer chain either directly or by means of a pendant alkyl or other functional group and Q′ is covalently bonded to the cylodextrin at the 2, 3 or 6 position thereby replacing either OR1, OR2 or OR3 group respectively;
• Q and Q′ are independently members selected from the group consisting of NR4, S, O, CO, CONH, and COO;
• Z is a member selected from the group consisting of an alkylene disulfide, [—(CH2)aS—S(CH2)a—], alkylene [—(CH2)a—], alkylene oxide (—[(CH2)aO]b(CH2)a—), or a short chained peptide where a is an integer of 1 to 10 and b is an integer of 1 to 20;
• R1, R2, R3 and R4 are independently members selected from the group consisting of H, alkyl (Cn′H2n′+1), alkenyl (Cn′+1H2(n′+1)−1) or acyl (Cn′H2n′+1CO) where n′ is an integer of 1 to 16;
• q is an integer of 5, 6 or 7;
• w is an integer such as to provide between 2 and 15 cyclodextrin units per 20 KD PEG backbone chain, and m and n are integers sufficient that when combined with w they represent a polyethylene oxide polymeric chain having the molecular weight of 5,000 to 70,000 with the proviso that monomeric units on the hydrophilic polymer chain containing the cyclodextrin units represented by w do not have to be consecutively joined but may be randomly or uniformly distributed along polymer chain.