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PLGA nanoparticles embedding molybdenum cluster salts: Influence of chemical composition on physico-chemical properties, encapsulation efficiencies, colloidal stabilities and in vitro release

Abstract : We present a screening of poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles embedding a series of inorganic molybdenum octahedral clusters intended for photodynamic therapy (PDT) of cancer. Three cluster compounds from 2 cluster units, [{Mo6Br8}Br6]2− and [{Mo6I8}(OOC2F5)6]2− were studied. [{Mo6Br8}Br6]2−cluster units are found in the soluble ternary salt Cs2[{Mo6Br8}Br6] (CMB) prepared by solid state chemistry at high temperature. In solution Cs+ cations are replaced by tetrabutyl ammonium cations (C4H9)4N+) to form the salt ((C4H9)4N)2[{Mo6Br8}Br6] (TBA2). [{Mo6I8}(OOC2F5)6]2− was prepared combining solid state and solution chemistries; it is paired with Cs+ cations to form Cs2[{Mo6I8}(OOC2F5)6] (CMIF). All tested cluster-based salts could efficiently be incorporated in PLGA nanoparticles as seen with encapsulation efficiencies always higher than 60%. Cluster loaded nanoparticles (CNPs) freshly prepared by solvent displacement method showed spherical shapes, zeta potential values between −20 and −47 mV, polydispersity index in the range 0.123–0.167 and sizes in the range 75–150 nm according to the cluster compound and the polymer-to-cluster mass ratio (P/C), suggesting a good cellular uptake. CNPs colloidal stability was maintened for 3 months when they were stored refrigerated and protected from light but the chemical stability was shorter, i.e. 4 weeks, 1 week and 1 day for CMIF, TBA2 and CMB, respectively, CMIF penta-fluoropropionate apical ligands being less rapidly substituted by hydroxyles groups than TBA2 and CMB halogen apical ligands. FT-IR analysis revealed the lack of strong chemical interaction between cluster compounds and polymer within the nanoparticles. An interesting quick cluster in vitro release driven by diffusion outside the nanoparticles porous matrix was observed for all cluster compounds when P/C ratio was ≤2.5 and only a higher P/C ratio not studied in this work (i.e. >5) could significantly affect the release of the encapsulated cluster compound. Photophysical properties of cluster compounds were preserved following PLGA incorporation. This work presents PLGA nanoparticles as a stable and efficient cluster compound delivery systems for further in vitro and vivo evaluations in cancer models.
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Submitted on : Monday, March 23, 2020 - 11:45:24 AM
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G Dollo, Y Boucaud, M Amela-Cortes, Y Molard, Stéphane Cordier, et al.. PLGA nanoparticles embedding molybdenum cluster salts: Influence of chemical composition on physico-chemical properties, encapsulation efficiencies, colloidal stabilities and in vitro release. International Journal of Pharmaceutics, Elsevier, 2020, 576, pp.119025. ⟨10.1016/j.ijpharm.2020.119025⟩. ⟨hal-02472161⟩

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