title: Bisphosphonate-functionalized hyaluronic acid showing selective affinity for osteoclasts as a potential treatment for osteoporosis.
abstract: 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.
authors.affiliation: Department of Chemistry, A Science for Life Laboratory, Polymer Chemistry Division, Uppsala University, Po Box 538, Lägerhyddsvägen 1, Uppsala SE 75121, Sweden. Jons.Hilborn@kemi.uu.se.
authors.forename: Sujit
authors.initials: S
authors.lastname: Kootala
authors.forename: Dmitri
authors.initials: D
authors.lastname: Ossipov
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.forename: Sander
authors.initials: S
authors.lastname: Leeuwenburgh
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation; D004164:Diphosphonates / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000737:chemistry* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D008970:Molecular Weight; D010010:Osteoclasts / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D011142:Polyvinyl Alcohol / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D018960:Hyaluronan Receptors; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate