title: The effect of poly(d,l-lactide-co-glycolide)-alendronate conjugate nanoparticles on human osteoclast precursors.
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.
authors.affiliation: a Laboratorio di Fisiopatologia Ortopedica e Medicina Rigenerativa, Istituto Ortopedico Rizzoli , via di Barbiano 1/10 , 40136 , Bologna , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cenni
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.forename: Caterina
authors.initials: C
authors.lastname: Fotia
authors.forename: Manuela
authors.initials: M
authors.lastname: Salerno
authors.forename: Dorotea
authors.initials: D
authors.lastname: Micieli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sarpietro
authors.forename: Rosario
authors.initials: R
authors.lastname: Pignatello
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000199:Actins / Q000378:metabolism; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry; D001859:Bone Neoplasms / Q000188:drug therapy; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D059748:Proteolysis / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000199:Actins; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019386:Alendronate