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: Jung-Kyo Cho, Ki-Yun Hong, Jung Won Park, Han-Kwang Yang, Soo-Chang Song
• Journal: Journal of drug targeting (J Drug Target) Vol. 19 Issue 4 Pg. 270-80 (May 2011) ISSN: 1029-2330 [Electronic] England
• PMID: 20608785 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Hydrogels
• Organophosphorus Compounds
• Platelet Endothelial Cell Adhesion Molecule-1
• Polymers
• poly(organophosphazene)
• Estradiol
• 2-Methoxyestradiol

Topics

• 2-Methoxyestradiol
• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Breast Neoplasms (drug therapy)
• Drug Carriers (chemistry)
• Estradiol (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Female
• Humans
• Hydrogels (chemistry)
• Immunohistochemistry
• Mice
• Neoplasms, Experimental (drug therapy)
• Organophosphorus Compounds (chemistry)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Polymers (chemistry)
• Rheology
• Solubility