Dual-functionalisation of gelatine nanoparticles with an anticancer platinum(ii)-bisphosphonate complex and mineral-binding alendronate

\u3cp\u3eIn order to improve the efficacy of therapeutic systems to treat bone tumours, novel drug delivery vehicles should be developed that have strong and specific affinity to mineralised tissue and at the same time are able to release anticancer molecules locally in a controlled and sustained manner. Recently, we developed mineral-binding gelatine nanoparticles with enhanced affinity to calcium phosphate by conjugating alendronate (ALN) molecules onto their surface. Herein, we have enhanced the functionality of these nanoparticles by rendering them potentially therapeutically active via covalent linking of an anticancer platinum-bisphosphonate (Pt-BP) complex. Different functionalisation schemes and molar ratios between reactants were screened and the effective functionalisation of gelatine nanoparticles with Pt-BP (or with both Pt-BP and ALN) was assessed. Our results revealed that the degree of functionalisation could be tailored by varying the molar ratio of Pt-BP and ALN relative to glutaraldehyde used as crosslinker. A sustained and tunable release of platinum as a function of the initial Pt-BP/ALN/glutaraldehyde molar ratio was achieved for both Pt-BP- and dual-functionalised gelatine nanoparticles. Moreover, dual-functionalised gelatine nanoparticles also displayed a high affinity to hydroxyapatite-coated surfaces thanks to the presence of ALN. Summarising, it was demonstrated that mineral-binding gelatine nanoparticles can be loaded with tailored amounts of anticancer molecules, which may benefit the development of bone-seeking carriers for targeted delivery of drugs to treat bone tumours.\u3c/p\u3

Hybrid particles derived from alendronate and bioactive glass for treatment of osteoporotic bone defects

\u3cp\u3eOsteoporosis is the most widespread metabolic bone disease which represents a major public health burden. Consequently, novel biomaterials with a strong capacity to regenerate osteoporotic bone defects are urgently required. In view of the anti-osteoporotic and osteopromotive efficacy of alendronate and 45S5 bioactive glass, respectively, we investigated the feasibility to synthesize novel hybrid particles by exploiting the strong interactions between these two compounds. Herein, we demonstrate the facile preparation of a novel class of hybrid particles of tunable morphology, chemical composition and structure. These hybrid particles (i) release alendronate and various inorganic elements (Ca, Na, Si, and P) in a controlled manner, (ii) exhibit a strong anti-osteoclastic effect in vitro, and (iii) stimulate regeneration of osteoporotic bone in vivo. Consequently, this novel class of hybrid biomaterials opens up new avenues of research on the design of bone substitutes with specific activity to facilitate regeneration of bone defects in osteoporotic patients.\u3c/p\u3

Hybrid particles derived from alendronate and bioactive glass for treatment of osteoporotic bone defects

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