Development of a Novel Transdermal Patch of Alendronate, a Nitrogen-ContainingBisphosphonate, for the Treatment of Bone Diseases

摘要

Bisphosphonates (BP) are widely used for thetreatment and prevention of bone diseases, includingPaget’s disease, hypercalcemia of malignancy, andpostmenopausal osteoporosis. Alendronate is aprimary amino bisphosphonate and one of the mostcommonly used members of this group. In this study,we developed a novel transdermal patch ofalendronate for the treatment of bone diseases. Theskin permeation of alendronate was sufficientlyobserved using our patch sytem for the treatment ofbone diseases. The plasma calcium level, which isan indicator of pharmacological effects ofalendronate, effectively decreased after applicationof alendronate patch in hypercalcemia model rats.Alendronate patch also effectively suppressed thedecrease of bone mineral density in osteoporosismodel rats. Although alendronate patch induced skindamage after its application, coadministration ofvarious anti-oxidants with alendronate completelysuppressed the alendronate-induced skin damage,while maintaining sufficient skin permeation ofalendronate. These findings indicate that ourtransdermal delivery system of alendronate is apromising approach to improve QOL and complianceof patients for the treatment of bone diseases.