title: Development of polymeric nanocarrier system for early detection and targeted therapeutic treatment of peri-implant osteolysis.
abstract: BACKGROUND
  Extensive research has implicated inflammation as a necessary and causative factor in the development of peri-implant osteolysis, suggesting that such an inflammatory response is the sentinel event for the process. The potential to impact the clinical course of this condition is hampered by the lack of an effective medical therapy, as well as a limited ability for early detection prior to radiographically evident osteolysis. Advances in nanotechnology have allowed for the production of engineered water-soluble nanocarriers, which exploit changes in the microvascular architecture for selective distribution to inflamed tissues. Evaluation of the uptake of the nanocarriers in sites of inflammation has elucidated a novel mechanism of cellular uptake and retention of these particles.
  
  
  OBJECTIVE
  The current review discusses the development of a novel, biocompatible, water-soluble nanocarrier utilizing copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA), conjugated to imaging and therapeutic agents for the detection and targeted treatment of inflammatory conditions.
  
  
  METHODS
  We performed Medline searches for the terms "periprosthetic osteolysis," "murine osteolysis model," "HPMA osteolysis," and "HPMA inflammation." These searches identified 631, 306, 1, and 6 articles, respectively. These were then manually searched for articles relevant to the development of mouse models for inflammatory osteolysis and the use of HPMA copolymer technology in mouse models of inflammation.
  
  
  RESULTS
  Promising results in a small animal model of osteolysis have demonstrated the capability for detection prior to the development of bone loss, and have highlighted the utility of nanocarriers for selective drug delivery to the affected tissues.
  
  
  CONCLUSIONS
  Challenges to the clinical translation of HPMA nanocarriers in peri-implant osteolysis remain, and the future research directions necessary for human clinical application are reviewed.
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.
authors.forename: P Edward
authors.initials: PE
authors.lastname: Purdue
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Levin
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198 USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sculco
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198 USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldring
keywords: HPMA; nanocarrier; optical imaging; periprosthetic osteolysis