Development of Polymeric Nanocarrier System for Early Detection and Targeted Therapeutic Treatment of Peri-Implant Osteolysis

Ed Purdue, PhD
Associate Research Scientist, Hospital for Special Surgery
Director, Osteolysis Research Laboratory, Hospital for Special Surgery

Adam S. Levin MD
Hospital for Special Surgery

Ke Ren
Department of Pharmaceutical Sciences, University of Nebraska Medical Center

Thomas P. Sculco MD
Surgeon-in-Chief, Hospital for Special Surgery
Professor of Orthopaedic Surgery, Weill Cornell Medical College

Dong Wang PhD
Department of Pharmaceutical Sciences, University of Nebraska Medical Center


Steven R. Goldring, MD

Steven R. Goldring, MD

Richard L. Menschel Research Chair, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College

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.

Purpose

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.

This article appears in HSS Journal: Volume 9, Number 1.
View the full article at springerlink.com.

About the HSS Journal

HSS Journal, an academic peer-reviewed journal published three times a year, February, July and October. The Journal accepts and publishes peer reviewed articles from around the world that contribute to the advancement of the knowledge of musculoskeletal diseases and disorders.

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