以預凝膠法製備磷酸鈣/海藻膠之核/殼奈米粒子並應用於酸鹼應答型的藥物釋放

Abstract

A new drug nanovehicle consisting of inorganic calcium phosphate (CaP) nanoparticle as core and organic alginate as shell (denoted as CaP@alginate) has been successfully synthesized via a pre-gel method and applied for pH-sensitive drug delivery systems (DDS). The CaP@alginate nanocomposite contains both advantages of CaP and alginate, where CaP provides pH-responsive degradability and alginate provides excellent biocompatibility and COOH functionality. Through the sequent addition of CaCl2 and phosphate solutions into alginate solution, CaP@alginate nanocomposites with controllable particle sizes (ranging from 160 to 650 nm) were obtained, and the core-shell structure of the CaP@alginate was observed under transmission electron microscopy (TEM). Rhodamine 6G (R6G), a positively charged and water-soluble dye, was selected as a model drug for pH-sensitive DDS. R6G was encapsulated in the nanocomposites during synthesis, and its loading efficiency can reach up to ca. 63.0%. The in vitro release behavior of the loaded R6G at different pH values was systematically studied, and the results indicated that more R6G molecules were released at lower pH conditions. For example, after release for 8 hours, the release amount of R6G at pH 2.0 was 2.53-fold of that at pH 7.4. We attributed this pH-sensitive release behavior to the dissolution of the CaP core at acidic conditions, and this pH-responsive behavior was expected to enhance the selective delivery of internal cargos. The results of MTT assay and confocal laser scanning microscopes indicated CaP@alg were successfully uptaken by HepG2 cells without apparent cytotoxicity. The CaP@alginate nanocomposites synthesized in this report show great potential as drug nanovehicles with high biocompatibility, specific targeting, and pH-responsible features for intracellular DDS in the future.