Cyclodextrins with one or more poly(ethylene glycol) units, inclusion compounds and drug delivery vehicles including the same, and methods of making and using the same

A method of synthesizing a pegylated beta-cyclodextrin, the method comprising:

• a) creating a tosylated monoalkoxy polyethylene glycol;
• and
• b) reacting the tosylated monoalkoxy polyethylene glycol with a deprotonated beta-cyclodextrin to form the pegylated beta-cyclodextrin, the pegylated beta-cyclodextrin having the structure:
• where each R is independently H or one or of the one or more monoalkoxy polyethylene glycols, a plurality of the Rs are H, each of the one or more monoalkoxy polyethylene glycols has the formula R′(OCH2CH2)n—, R′ is an alkyl group, and n is such that the group of the formula R′(OCH2CH2)n— has a minimum molecular weight of 200 g/mol.

A method of improving the water solubility of a beta-cyclodextrin, comprising:

• a) linking a monoalkoxy polyethylene glycol to the beta-cyclodextrin through an ether bond to form a compound having the structure:
• wherein one or of the one or more monoalkoxy polyethylene glycols, a plurality of the Rs are H, each of the one or two Rs in the compound is a monoalkoxy polyethylene glycol having the formula R′(OCH2CH2)n—, R′ is an alkyl group, the remaining Rs are H, and n is such that the group of the formula R′(OCH2CH2)n— has a molecular weight of 300 to 5000 g/mol;
• and
• b) dissolving the compound in water.

A method of synthesizing an inclusion compound containing a drug and a compound comprising a beta-cyclodextrin and one or more monoalkoxy polyethylene glycols linked thereto through an ether bond, having the structure:

• where each R is independently H or one of the one or more monoalkoxy polyethylene glycols, a plurality of the Rs are H, each of the one or more monoalkoxy polyethylene glycols has the formula R′(OCH2CH2)n—, R′ is an alkyl group, and n is such that the group of the formula R′(OCH2CH2)n— has a minimum molecular weight of 200 g/mol, the method comprising:
• a) dissolving the compound in deionized water or an aqueous buffer solution to form a solution;
• and
• b) mixing the solution with the drug to form the inclusion compound.

A method of delivering a drug to a patient in need thereof, comprising:

• a) creating an inclusion compound comprising the drug and a compound comprising a beta-cyclodextrin and one or more monoalkoxy polyethylene glycols linked thereto through an ether bond, having the structure:
• where each R is independently H or one of the one or more monoalkoxy polyethylene glycols, a plurality of the Rs are H, each of the one or more monoalkoxy polyethylene glycols has the formula R′(OCH2CH2)n—, R′ is an alkyl group, and n is such that the group of the formula R′(OCH2CH2)n— has a minimum molecular weight of 200 g/mol;
• and
• b) administering an effective amount of the drug in the inclusion compound to the patient.