A novel biomaterial for osteotropic drug nanocarriers: Synthesis and biocompatibility evaluation of a PLGA-ALE conjugate

Rosario Pignatello, Elisabetta Cenni, Dorotea Micieli, Caterina Fotia, Manuela Salerno, Donatella Granchi, Sofia Avnet, Maria G. Sarpietro, Francesco Castelli, Nicola Baldini

Research output: Contribution to journalArticle

Abstract

Background & aims: Osteotropic drug-delivery systems have been proposed as a means to provide drugs with affinity to bone tissues. Drugs or proteins have been linked chemically to bone-seeking agents, such as bisphosphonates (BPs); alternatively, drug-loaded nanoparticles have been used to target specific tissues, such as tumor areas. In our current research, these approaches were merged by synthesizing a novel bone-seeking polymer conjugate, from which targetable nanoparticles can be produced. Materials & methods: An amino-BP, alendronate (ALE) was bound covalently to a biodegradable polymer, poly(lactic-co-glycolide) (PLGA), containing a free end carboxylic group. Blood compatibility and cytotoxicity were assessed in vitro. Results & discussion: By a classical solvent-evaporation method, nanoparticles with a mean size of 200-300 nm were prepared from the conjugate; sterilization was achieved by γ-irradiation, confirming their potential as injectable drug nanocarriers. Owing to the presence of the BP residue, PLGA-ALE nanoparticles were adsorbed onto hydroxyapatite to a higher extent than pure PLGA nanoparticles. The PLGA-ALE conjugate did not induce either hemolysis or alterations of the plasmatic phase of coagulation, or cytotoxic effects on endothelial cells and trabecular osteoblasts. Conclusion: The prepared conjugate represents a novel biomaterial that is able to provide nanoparticles, which can be further loaded with drugs, such as anticancer agents, and addressed to osteolytic or other bone diseases.

Original languageEnglish
Pages (from-to)161-175
Number of pages15
JournalNanomedicine
Volume4
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Alendronate
  • Biocompatibility
  • Bisphosphonates
  • Nanoparticles
  • ODDS
  • Osteotropic drug-delivery systems
  • Poly(lactide-co-glycolide)
  • Polymer conjugates

ASJC Scopus subject areas

  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Development

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