Bisphosphonates as a foundation of drug delivery to bone.
Bisphosphonates are organic analogues of pyrophosphate that are resistant to hydrolysis. Bisphosphonates exhibit an exceptional affinity to bone, which led to exploration of their utility for targeting pharmacological agents to bone. Among the pharmacological agents explored for bone delivery are radioisotopes, anti-neoplastic drugs, agents intended for augmentation of systemic bone mass, anti-inflammatory drugs and proteins. This review is intended to provide a summary of the literature on bisphosphonate-based drug delivery. A survey of therapeutic agents designed for bone targeting was provided in the first part of this review. Special emphasis was placed on the preclinical performance of the developed agents. In the second part, several aspects that were considered critical for the success of bisphosphonate-based drug delivery were explored. These aspects were oral bioavailability, protein binding of BPs, the nature of a BP-drug linkage and the choice of bone-affinity molecule. This article concludes with the author's perspective on the future of bisphosphonate-based drug delivery.
Uludag
Hasan
H
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, T6G 2G6, Canada. hasan.uludag@ualberta.ca
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D001847:Bone Diseases / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates; D004337:Drug Carriers; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004164:Diphosphonates; D004337:Drug Carriers; D011506:Proteins; D011868:Radioisotopes