The effect of poly(D,L-lactide-co-glycolide)-alendronate conjugate nanoparticles on human osteoclast precursors

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

Research output: Contribution to journalArticle

Abstract

Nanoparticles (NPs) formed from polymers conjugated with bisphosphonates (BPs) allow the bone targeting of loaded drugs, such as doxorubicin, for the treatment of skeletal tumours. The additional antiosteoclas-tic effect of the conjugated BP could contribute to the inhibition of tumour-associated bone degradation. With this aim, we have produced NPs made of poly(D,L-lactide-co- glycolide) (PLGA) conjugated with al-endronate (ALE). To show if ALE retained the antiosteoclastic properties after the conjugation with PLGA and the production of NPs, we treated human osteoclasts, derived from circulating precursors, with PLGA- ALE NPs and compared the effects on actin ring generation, apoptosis and type-I collagen degradation with those of free ALE and with NPs made of pure PLGA. PLGA-ALE NPs disrupted actin ring, induced apopto-sis and inhibited collagen degradation. Unexpectedly, also NPs made of pure PLGA showed similar effects. Therefore, we cannot exclude that in addition to the observed antiosteoclastic activity dependent on ALE in PLGA-ALE NPs, there was also an effect due to pure PLGA. Still, as PLGA-ALE NPs are intended for the loading with drugs for the treatment of osteolytic bone metastases, the additional antiosteoclastic effect of PLGA-ALE NPs, and even of PLGA, may contribute to the inhibition of the disease-associated bone degradation.

Original languageEnglish
Pages (from-to)1285-1300
Number of pages16
JournalJournal of Biomaterials Science, Polymer Edition
Volume23
Issue number10
DOIs
Publication statusPublished - 2012

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Keywords

  • Bisphosphonate
  • Bone targeting
  • Nanoparticle
  • Osteoclast
  • Poly(D,L-lactide-co-glycolide)

ASJC Scopus subject areas

  • Biophysics
  • Biomaterials
  • Bioengineering
  • Biomedical Engineering

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