title: Injectable delivery system of 2-methoxyestradiol for breast cancer therapy using biodegradable thermosensitive poly(organophosphazene) hydrogel.
abstract: 2-Methoxyestradiol (2-ME) has been reported to have antiangiogenic and antitumor activity. Its biomedical application is limited due to its poor water solubility resulting in its low bioavailability. Poly(organophosphazenes) containing l-isoleucine ethyl ester, ethyl-2-(O-glycyl)lactate, and α-amino-ω-methoxy-poly(ethylene glycol) 550 were synthesized having M(W) of 35-38 kDa and polydispersity index of 2.38-2.73. Using a viscometer, the thermosensitivity useful for locally injectable drug delivery was verified. The aqueous polymer solution showed a sol state at a low temperature and transformed to a gel state at body temperature. The polymer solution (10 wt%) enhanced the solubility of 2-ME by about 10(4) times compared to that of phosphate buffered saline. 2-ME was released from the hydrogel mainly by diffusion, hydrophobic interaction, and surface erosion of the matrix. This release profile could be confirmed through an in vitro release test as a function of polymers and the concentration of 2-ME in hydrogels. By monitoring tumor volume and CD31 immunohistochemical staining in mouse orthotopic breast tumor (MDA-MB-231) model, it was found that the hydrogel containing a relatively low concentration (15 mg/kg) of 2-ME showed the improved antitumor and antiangiogenic activity relative to the original formulation. This research suggests that the developed formulation of poly(organophosphazenes) may have injectable carrier potentials for 2-ME and other lipophilic drugs.
authors.affiliation: Life/Health Division, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, Korea.
authors.forename: Jung-Kyo
authors.initials: JK
authors.lastname: Cho
authors.forename: Ki-Yun
authors.initials: KY
authors.lastname: Hong
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Soo-Chang
authors.initials: SC
authors.lastname: Song
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007150:Immunohistochemistry; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D012212:Rheology; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D020100:Hydrogels; D009943:Organophosphorus Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011108:Polymers; C515246:poly(organophosphazene); D004958:Estradiol; D000077584:2-Methoxyestradiol