Bisphosphonate-functionalized hyaluronic acid showing selective affinity for osteoclasts as a potential treatment for osteoporosis.

Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101593571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-4849 (Electronic) Linking ISSN: 20474830 NLM ISO Abbreviation: Biomater Sci Subsets: MEDLINE

Original Publication: Cambridge, UK : Royal Society of Chemistry

Biocompatible Materials/*chemistry ; Bone Density Conservation Agents/*pharmacology ; Bone Resorption/*metabolism ; Diphosphonates/*chemistry ; Diphosphonates/*pharmacology ; Drug Delivery Systems/*methods ; Fluorescein-5-isothiocyanate/*chemistry ; Hyaluronan Receptors/*chemistry ; Hyaluronic Acid/*administration & dosage ; Hyaluronic Acid/*chemistry ; Osteoclasts/*chemistry ; Osteoclasts/*cytology ; Osteoporosis/*drug therapy ; Polyvinyl Alcohol/*chemistry; Bone Density Conservation Agents/chemistry ; Bone Density Conservation Agents/pharmacokinetics ; Cell Differentiation ; Fluorescein-5-isothiocyanate/metabolism ; Hyaluronan Receptors/metabolism ; Hyaluronic Acid/pharmacology ; Molecular Weight ; Osteoclasts/metabolism ; Osteoporosis/metabolism

Current treatments for osteoporosis involve the administration of high doses of bisphosphonates (BPs) over a number of years. However, the efficiency of the absorption of these drugs and specificity towards targeted osteoclastic cells is still suboptimal. In this study, we have exploited the natural affinity of high (H) and low (L) molecular-weight hyaluronic acid (HA) towards a cluster of differentiation 44 (CD44) receptors on osteoclasts to use it as a biodegradable targeting vehicle. We covalently bonded BP to functionalised HA (HA-BP) and found that HA-BP conjugates were highly specific to osteoclastic cells and reduced mature osteoclast numbers significantly more than free BP. To study the uptake of HA-BP, we fluorescently derivatised the polymer-drug with fluorescein B isothiocyanate (FITC) and found that L-HA-BP could seamlessly enter osteoclastic cells. Alternatively, we tested polyvinyl alcohol (PVA) as a synthetic polymer delivery vehicle using similar chemistry to link BP and found that osteoclast numbers did not reduce in the same way. These findings could pave the way for biodegradable polymers to be used as vehicles for targeted delivery of anti-osteoporotic drugs.

Erratum in: Biomater Sci. 2015 Oct 15;3(10):1414. (PMID: 26247158)

0 (Biocompatible Materials)
0 (Bone Density Conservation Agents)
0 (Diphosphonates)
0 (Hyaluronan Receptors)
9002-89-5 (Polyvinyl Alcohol)
9004-61-9 (Hyaluronic Acid)
I223NX31W9 (Fluorescein-5-isothiocyanate)

Date Created: 20150730 Date Completed: 20170112 Latest Revision: 20171116

20240829

10.1039/c5bm00096c

26222035