The Effect of Poly(d,l-Lactide-co-Glycolide)-Alendronate Conjugate Nanoparticles on Human Osteoclast Precursors

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 antiosteoclastic effect of the conjugated BP could contribute to the inhibition of tumour-associated bon...

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Bibliographic Details
Published in:Journal of biomaterials science. Polymer ed. 2012-01, Vol.23 (10), p.1285-1300
Main Authors: Cenni, Elisabetta, Avnet, Sofia, Granchi, Donatella, Fotia, Caterina, Salerno, Manuela, Micieli, Dorotea, Sarpietro, Maria Grazia, Pignatello, Rosario, Castelli, Francesco, Baldini, Nicola
Format: Article
Language:English
Subjects:
Apoptosis
Biocompatibility
Biomedical materials
bisphosphonate
bone targeting
Bones
Degradation
Drugs
Inhibition
Nanoparticle
osteoclast
poly(d,l-lactide-co-glycolide)
Precursors
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Summary: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 antiosteoclastic 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 alendronate (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 apoptosis 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.
ISSN:0920-5063
1568-5624
DOI:10.1163/092050611X580373