1. The effect of poly(d,l-lactide-co-glycolide)-alendronate conjugate nanoparticles on human osteoclast precursors.
- Author
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Cenni E, Avnet S, Granchi D, Fotia C, Salerno M, Micieli D, Sarpietro MG, Pignatello R, Castelli F, and Baldini N
- Subjects
- Actins metabolism, Alendronate chemistry, Apoptosis drug effects, Bone Density Conservation Agents chemistry, Bone Neoplasms drug therapy, Cells, Cultured, Collagen Type I metabolism, Dose-Response Relationship, Drug, Humans, Lactic Acid chemistry, Osteoclasts physiology, Polyglycolic Acid chemistry, Polylactic Acid-Polyglycolic Acid Copolymer, Proteolysis drug effects, Proton Magnetic Resonance Spectroscopy, Alendronate administration & dosage, Bone Density Conservation Agents administration & dosage, Lactic Acid pharmacology, Nanoparticles chemistry, Osteoclasts drug effects, Polyglycolic Acid pharmacology
- 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 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.
- Published
- 2012
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