Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats

Ziyad S. Haidar, Reggie C. Hamdy, Maryam Tabrizian

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

A hybrid, localized and release-controlled delivery system for bone growth factors consisting of a liposomal core incorporated into a shell of alternating layer-by-layer self-assembled natural polyelectrolytes has been formulated. Hydrophilic, monodisperse, spherical and stable cationic nanoparticles (≤350 nm) with an extended shelf-life resulted. Cytocompatibility was previously assayed with MC3T3-E1.4 mouse preosteoblasts showing no adverse effects on cell viability. In this study, the in vivo biocompatibility of unloaded and loaded nanoparticles with osteogenic protein-1 or OP-1 was investigated. Young male Wistar rats were injected intramuscularly and monitored over a period of 10 weeks for signs of inflammation and/or adverse reactions. Blood samples (600 μL/collection) were withdrawn followed by hematological and biochemical analysis. Body weight changes over the treatment period were noted. Major organs were harvested, weighed and examined histologically for any pathological changes. Finally, the injection site was identified and examined immunohistochemically. Overall, all animals showed no obvious toxic health effects, immune responses and/or change in organ functions. This hybrid core-shell nanoparticulate delivery system localizes the effect of the released bioactive load within the site of injection in muscle with no significant tissue distress. Hence, a safe and promising carrier for therapeutic growth factors and possibly other biomolecules is presented.
Original languageAmerican English
Pages (from-to)2746-2754
Number of pages9
JournalBiomaterials
Volume31
Issue number10
DOIs
StatePublished - 1 Apr 2010
Externally publishedYes

Keywords

  • Biocompatibility
  • BMP
  • Drug delivery
  • Foreign body response
  • Haemocompatibility
  • Nanoparticle

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