Hydrolytically releasable prodrugs for sustained release nanoparticle formulations

• US 9,233,163 B2
• Filed: 12/28/2011
• Issued: 01/12/2016
• Est. Priority Date: 12/28/2010
• Status: Active Grant

• Current Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Original Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Inventors: Alferiev, Ivan, Chorny, Michael, Levy, Robert J.
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US13/976,776
• Publication Number:
  US 20130296285A1
• Time in Patent Office: 1,476 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 47/551 one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
• CPC Class Codes: A61K 47/554 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran

Abstract

A prodrug according to formula (I) wherein R² is a residue of a drug, said drug having a hydroxyl group by which the COOR² group is formed; Z is O or NH; m is 0 or 1; and R³ is an organic moiety comprising a lipophilic group or a residue of a polymer, provided that Z is 0 if the polymer is carboxymethyl dextran. A system includes a plurality of magnetic nanoparticles including a prodrug as described above, a stent and a source of uniform magnetic field capable of producing temporary magnetization of the stent and/or the magnetic nanoparticles. A method of treating a medical condition with a drug includes administering to a patient in need of the drug a prodrug as described above, the prodrug being capable of releasing the drug in the patient after the administration step.

Claims

1. A system comprising a plurality of magnetic nanoparticles comprising a prodrug according to formula (I), an implantable medical device, and a source of uniform magnetic field capable of producing temporary magnetization of the implantable medical device and/or the magnetic nanoparticles,

2. The system according to claim 1, wherein R³—

CO is a residue of a carboxylic acid having from 8 to 30 carbon atoms.

3. The system according to claim 1, wherein R³—

CO is a residue of a carboxylic acid selected from the group consisting of palmitic acid, stearic acid, oleic acid, ricinoleic acid, docosahexaenoic acid and retinoic acid.

4. The system according to claim 1, wherein R³ comprises a cholesterol or tocopherol moiety.