Targeted delivery to bone and mineral deposits using bisphosphonate ligands
| Autor: | Ryan K. Roeder, Tracy Vargo-Gogola, Lisa E. Cole |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Pathology medicine.medical_specialty media_common.quotation_subject medicine.medical_treatment Pharmaceutical Science 02 engineering and technology Ligands Bone and Bones 03 medical and health sciences Drug Delivery Systems In vivo medicine Animals Humans media_common Bone mineral Minerals Diphosphonates Bone cancer Chemistry Bisphosphonate 021001 nanoscience & nanotechnology medicine.disease Ligand (biochemistry) 030104 developmental biology Drug Design Drug delivery Cancer research 0210 nano-technology |
| Zdroj: | Advanced Drug Delivery Reviews. 99:12-27 |
| ISSN: | 0169-409X |
| DOI: | 10.1016/j.addr.2015.10.005 |
| Popis: | The high concentration of mineral present in bone and pathological calcifications is unique compared with all other tissues and thus provides opportunity for targeted delivery of pharmaceutical drugs, including radiosensitizers and imaging probes. Targeted delivery enables accumulation of a high local dose of a therapeutic or imaging contrast agent to diseased bone or pathological calcifications. Bisphosphonates (BPs) are the most widely utilized bone-targeting ligand due to exhibiting high binding affinity to hydroxyapatite mineral. BPs can be conjugated to an agent that would otherwise have little or no affinity for the sites of interest. This article summarizes the current state of knowledge and practice for the use of BPs as ligands for targeted delivery to bone and mineral deposits. The clinical history of BPs is briefly summarized to emphasize the success of these molecules as therapeutics for metabolic bone diseases. Mechanisms of binding and the relative binding affinity of various BPs to bone mineral are introduced, including common methods for measuring binding affinity in vitro and in vivo. Current research is highlighted for the use of BP ligands for targeted delivery of BP conjugates in various applications, including (1) therapeutic drug delivery for metabolic bone diseases, bone cancer, other bone diseases, and engineered drug delivery platforms; (2) imaging probes for scintigraphy, fluorescence, positron emission tomography, magnetic resonance imaging, and computed tomography; and (3) radiotherapy. Last, and perhaps most importantly, key structure-function relationships are considered for the design of drugs with BP ligands, including the tether length between the BP and drug, the size of the drug, the number of BP ligands per drug, cleavable tethers between the BP and drug, and conjugation schemes. |
| Databáze: | OpenAIRE |
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