Preparation and evaluation of highly dispersible and Ca2+ level responsive PEGylated calcium phosphate nanoparticle with PEG-block-poly(4-vinylbenzylphosphonate) for the application of drug carrier:

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PEGylated calcium phosphate nanoparticles (CaPNPs) were prepared through the simple mixing of calcium and phosphate solutions in the presence of a PEG-block-poly(4-vinylbenzylphosphonate) (PEG-b-PVBP). The PEG-b-PVBP possesses the phosphonate side chains and the hydrophobic polystyrene segment which enhance the stability of the PEG brush layer on the CaPNP surface. The size of CaPNPs was controlled within the range of several tens of nanometer depending on the [PVBP unit]/[phosphate ion] feed-molar ratio upon the CaP coprecipitation reaction. The obtained CaPNPs showed excellent colloidal stability and it was sustained even after the lyophilization. In vitro cell cytotoxicity assay suggested that the CaPNPs do not induce serious cytotoxicity in the murine colon adenocarcinoma 26 (C-26) cells. Light scattering study revealed that the CaPNPs can be dissolved into the low Ca2+ condition ([Ca2+] = 0.1 mM). Since intracellular Ca2+ concentration is four orders of magnitude lower than the extracellular one, the Ca2+ concentration responsive dissolution behavior of CaPNPs is promising for the intracellular delivery of therapeutic materials.
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