Bisphosphonate conjugation for bone specific drug targeting

Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effecti...

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Main Authors: Kristen B. Farrell, Alexander Karpeisky, Douglas H. Thamm, Shawn Zinnen
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Bone Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S235218721830041X
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author Kristen B. Farrell
Alexander Karpeisky
Douglas H. Thamm
Shawn Zinnen
author_facet Kristen B. Farrell
Alexander Karpeisky
Douglas H. Thamm
Shawn Zinnen
author_sort Kristen B. Farrell
collection DOAJ
description Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types. The bisphosphonate molecule class binds specifically to hydroxyapatite and inhibits osteoclast resorption of bone, providing direct treatment for degenerative bone disorders, and as emerging evidence suggests, cancer. These bone-binding molecules also provide the opportunity to deliver other drugs specifically to bone by bisphosphonate conjugation. Bisphosphonate bone-targeted therapies have been successful in treatment of osteoporosis, primary and metastatic neoplasms of the bone, and other bone disorders, as well as refining bone imaging. In this review, we focus upon the use of bisphosphonate conjugates with antineoplastic agents, and overview bisphosphonate based imaging agents, nanoparticles, and other drugs. We also discuss linker design potential and the current state of bisphosphonate conjugate research progress. Ongoing investigations continue to expand the possibilities for bone-targeted therapeutics and for extending their reach into clinical practice. Keywords: Bisphosphonates, Bone-targeting, Drug conjugates, Cancer induced bone disease, Infection, Osteomyelitis
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spelling doaj.art-22c276b4b5674c1284daf05148ff0c7b2022-12-21T17:30:25ZengElsevierBone Reports2352-18722018-12-0194760Bisphosphonate conjugation for bone specific drug targetingKristen B. Farrell0Alexander Karpeisky1Douglas H. Thamm2Shawn Zinnen3MBC Pharma Inc., 12635 East Montview Blvd., Aurora, CO 80045-0100, United States of AmericaMBC Pharma Inc., 12635 East Montview Blvd., Aurora, CO 80045-0100, United States of AmericaFlint Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523-1620, United States of AmericaMBC Pharma Inc., 12635 East Montview Blvd., Aurora, CO 80045-0100, United States of America; Corresponding author.Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types. The bisphosphonate molecule class binds specifically to hydroxyapatite and inhibits osteoclast resorption of bone, providing direct treatment for degenerative bone disorders, and as emerging evidence suggests, cancer. These bone-binding molecules also provide the opportunity to deliver other drugs specifically to bone by bisphosphonate conjugation. Bisphosphonate bone-targeted therapies have been successful in treatment of osteoporosis, primary and metastatic neoplasms of the bone, and other bone disorders, as well as refining bone imaging. In this review, we focus upon the use of bisphosphonate conjugates with antineoplastic agents, and overview bisphosphonate based imaging agents, nanoparticles, and other drugs. We also discuss linker design potential and the current state of bisphosphonate conjugate research progress. Ongoing investigations continue to expand the possibilities for bone-targeted therapeutics and for extending their reach into clinical practice. Keywords: Bisphosphonates, Bone-targeting, Drug conjugates, Cancer induced bone disease, Infection, Osteomyelitishttp://www.sciencedirect.com/science/article/pii/S235218721830041X
spellingShingle Kristen B. Farrell
Alexander Karpeisky
Douglas H. Thamm
Shawn Zinnen
Bisphosphonate conjugation for bone specific drug targeting
Bone Reports
title Bisphosphonate conjugation for bone specific drug targeting
title_full Bisphosphonate conjugation for bone specific drug targeting
title_fullStr Bisphosphonate conjugation for bone specific drug targeting
title_full_unstemmed Bisphosphonate conjugation for bone specific drug targeting
title_short Bisphosphonate conjugation for bone specific drug targeting
title_sort bisphosphonate conjugation for bone specific drug targeting
url http://www.sciencedirect.com/science/article/pii/S235218721830041X
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