Bisphosphonate-decorated lipid nanoparticles designed as drug carriers for bone diseases

J Biomed Mater Res A. 2012 Mar;100(3):684-93. doi: 10.1002/jbm.a.34002. Epub 2011 Dec 30.


A conjugate of distearoylphosphoethanolamine-polyethylene glycol with 2-(3-mercaptopropylsulfanyl)-ethyl-1,1-bisphosphonic acid (thiolBP) was synthesized and incorporated into micelles and liposomes to create mineral-binding nanocarriers for therapeutic agents. The micelles and liposomes were used to encapsulate the anticancer drug doxorubicin (DOX) and a model protein lysozyme (LYZ) by using lipid film hydration (LFH) and reverse-phase evaporation vesicle (REV) methods. The results indicated that the micelles and LFH-derived liposomes were better at DOX loading than the REV-derived liposomes, while the REV method was preferable for encapsulating LYZ. The affinity of the micellar and liposomal formulations to hydroxyapatite (HA) was assessed in vitro, and the results indicated that all the thiolBP-incorporated nanocarriers had stronger HA affinity than their counterparts without thiolBP. The thiolBP-decorated liposomes also displayed a strong binding to a collagen/HA composite scaffold in vitro. More importantly, thiolBP-decorated liposomes gave increased retention in the collagen/HA scaffolds after subcutaneously implantation in rats. The designed liposomes were able to entrap the bone morphogenetic protein-2 in a bioactive form, indicating that the proposed nanocarriers could deliver bioactive factors locally in mineralized scaffolds for bone tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Bone Density Conservation Agents* / chemistry
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Diseases / drug therapy*
  • Bone and Bones / metabolism
  • Diphosphonates* / chemistry
  • Diphosphonates* / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Delivery Systems / methods*
  • Female
  • Lipids / chemistry*
  • Liposomes / chemistry
  • Materials Testing
  • Micelles
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley


  • Biocompatible Materials
  • Bone Density Conservation Agents
  • Diphosphonates
  • Drug Carriers
  • Lipids
  • Liposomes
  • Micelles