Conjugation of nanoparticles (NPs) with bisphosphonates allows for the specific targeting of drugs to skeleton, like as doxorubicin for the treatment of bone tumours. With this aim, we have previously synthesized poly(D,L-lactide-co-glycolide) (PLGA) NPs conjugated with alendronate (ALE). To show if ALE bound to PLGA (PLGA-ALE) retains its antiosteoclastic properties, we treated human osteoclasts derived from circulating precursors with PLGA-ALE NPs and compared the effects on apoptosis and osteoclast-mediated type I collagen degradation with those of soluble ALE and with NPs made of pure PLGA. PLGA-ALE NPs had similar effects to soluble ALE, because they induced apoptosis and inhibited collagen degradation at a similar extent. However, similar results were also noticed with NPs made of pure PLGA. 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 complementary antiosteoclastic effect of PLGA-ALE NPs may contribute to the inhibition of the disease-associated bone degradation.
The effect of poly(D,L-lactide-co-glycolide)-alendronate conjugate nanoparticles on human osteoclast precursors.
SARPIETRO, MARIA GRAZIA;PIGNATELLO, Rosario;CASTELLI, Francesco;
2012-01-01
Abstract
Conjugation of nanoparticles (NPs) with bisphosphonates allows for the specific targeting of drugs to skeleton, like as doxorubicin for the treatment of bone tumours. With this aim, we have previously synthesized poly(D,L-lactide-co-glycolide) (PLGA) NPs conjugated with alendronate (ALE). To show if ALE bound to PLGA (PLGA-ALE) retains its antiosteoclastic properties, we treated human osteoclasts derived from circulating precursors with PLGA-ALE NPs and compared the effects on apoptosis and osteoclast-mediated type I collagen degradation with those of soluble ALE and with NPs made of pure PLGA. PLGA-ALE NPs had similar effects to soluble ALE, because they induced apoptosis and inhibited collagen degradation at a similar extent. However, similar results were also noticed with NPs made of pure PLGA. 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 complementary antiosteoclastic effect of PLGA-ALE NPs may contribute to the inhibition of the disease-associated bone degradation.File | Dimensione | Formato | |
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Cenni et al - J Biomat Sci 23 (2012) 1285–1300.pdf
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