Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

Zaineb A F Albayati; Manjula Sunkara; Suzannah M Schmidt-Malan; Melissa J Karau; Andrew J Morris; James M Steckelberg; Robin Patel; Philip J Breen; Mark S Smeltzer; K Grant Taylor; Kevyn E Merten; William M Pierce; Peter A Crooks

doi:10.1128/AAC.01609-15

Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

Antimicrob Agents Chemother. 2015 Dec 14;60(3):1865-8. doi: 10.1128/AAC.01609-15.

Affiliations

¹ College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
² Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, USA.
³ Department of Laboratory Medicine and Pathology Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Laboratory Medicine and Pathology Mayo Clinic, Rochester, Minnesota, USA Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁷ Department of Chemistry, University of Louisville, Louisville, Kentucky, USA.
⁸ Pradama, Inc., Louisville, Kentucky, USA.
⁹ Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA wmpier01@louisville.edu pacrooks@uams.edu.
¹⁰ College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA wmpier01@louisville.edu pacrooks@uams.edu.

Abstract

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / pharmacokinetics
Anti-Bacterial Agents / therapeutic use*
Bone and Bones / metabolism
Debridement
Disease Models, Animal
Drug Carriers / therapeutic use*
Durapatite / metabolism*
Humans
Osteomyelitis / drug therapy*
Osteomyelitis / microbiology
Polyethylene Glycols / chemistry
Rats
Staphylococcal Infections / drug therapy
Staphylococcal Infections / microbiology
Staphylococcus aureus / drug effects
Vancomycin / administration & dosage*
Vancomycin / pharmacokinetics*
Vancomycin / therapeutic use

Substances

Anti-Bacterial Agents
Drug Carriers
Polyethylene Glycols
Vancomycin
Durapatite

Grants and funding

R01 AR056647/AR/NIAMS NIH HHS/United States