Could local delivery of bisphosphonates be a new therapeutic choice for hemangiomas?

Abstract

Hemangiomas are endothelial neoplasms that affected about 8-12% of one-year-old children. Their life cycle is characterized by a rapid endothelial proliferation phase, followed by a slow involution phase. About 10% of the hemangiomas will cause functional complications or psychological concern requiring active treatments. Current therapy methods, such as intra-lesional or systemic administration of corticosteroids, systemic interferon treatment, or surgery, are diverse but uncertainty. To date, the etiology of hemangiomas is still controversial. However, general consensus on the importance of the endothelial cells leads hemangioma pathogenesis to angiogenesis. Thus, local delivery of anti-angiogenic agents may be of great interest for the treatment of hemangiomas. Bisphosphonates are potent in inhibiting osteoclast activity and promoting apoptosis, which are widely used for the treatment of osteoporosis and osteolysis diseases with minor adverse side effects. In addition to its anti-osteolytic effect, bisphosphonates are currently shown to be capable of anti-angiogenesis and induction of apoptosis in tumor cells. Experimental evidences demonstrated that bisphosphonates can inhibit capillary tube formation and vessel sprouting by impairing endothelial proliferation and migration, as well as reducing the serum fibroblast growth factor-2 and vascular endothelial growth factor. Moreover, it is not impossible to deliver bisphosphonates to local lesion by a new local drug delivery system (DDS), which employed the biocompatible calcium phosphate as the drug carriers for clinical use. This local drug delivery system is a suitable carrier for loading and releasing of bioactive bisphosphonates. Therefore, we hypothesis that local deliver of bisphosphonates by fine calcium phosphate particles may be a potential treatment of hemangiomas. By employing proper calcium phosphate particles, bioactive bisphosphonates will be gradually released and exert their anti-angiogenesis effect, destructing rapid proliferation of epithelial cells and promoting the involution of hemangiomas without systematic adverse side effects.