localized delivery of 1 , 25 d 3 directly 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 d 3 have also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1 , 25 d 3 analogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as alzheimer &# 39 ; 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 d 3 were incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1 , 3 - bispropane and sebacic acid 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 3 &# 39 ; s antiangiogenic , antiproliferative , and transcriptional regulating activities .