Mark C Watts
Physician at Tremont Pl, Denver, CO

2008026, Oct 23, 2008

Jun 30, 2008

12/165036

Martin Burke - Champaign IL, US
Maria-Christina White - Champaign IL, US
Mark C. Watts - Denver CO, US
Jae Kyoo Lee - North Andover MA, US
Betty M. Tyler - Catonsville MD, US
Gary H. Posner - Baltimore MD, US
Henry Brem - Owings Mills MD, US

A61K 31/59, A61K 9/10, A61P 35/00, A61P 25/28

424486, 514167

Localized delivery of 1,25 Ddirectly to a target area using biodegradable polymeric matrices maximizes the efficacy of this drug while minimizing systemic exposure and toxicity. Anticalcemic analogs of 1,25 Dhave also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1,25 Danalogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as Alzheimer's disease as well as to maximize the efficacy of these analogs in the treatment of systemic malignancies. The therapeutic efficacy of these formulations was demonstrated through a variety of studies in vitro and in vivo. Hybrid analogs of 1,25 Dwere incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20:80 molar ratio. In addition to providing improved treatments for malignancies and neurodegenerative disorders, the spatial localization and high reproducibility of this controlled delivery methodology presents a unique opportunity to study in vivo the poorly understood mechanisms of 1,25 D's antiangiogenic, antiproliferative, and transcriptional regulating activities.