Synthesis and characterization of CaCO3-biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin.

V. E. BOSIO; M. L. CACICEDO; B. CALVIGNAC; I. LEON; T. BEUVIER; F. BOURY; G.R. CASTRO

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 123 p. 158 - 169

0927-7765

Doxorubicin (Dox) is a hydrophilic drug extensively used for treatment of breast, lung, and ovarian cancer, among others; it is highly toxic and can cause serious side effects on nontargeted tissues. We developed and studied a hybrid nanoporous microparticle (hNP) carrier based on calcium carbonate and biopoly- mers derivatized with folic acid (FA) and containing Dox as a chemotherapeutic drug model. The hNPs were characterized by X-ray diffraction, and Raman and Fourier transform infrared (FTIR) spectroscopies. The X-ray diffraction patterns of calcium carbonate particles showed about 30?70% vaterite?calcite poly- morphisms and up to 95% vaterite, depending on the absence or the presence of biopolymers as well as their type. Scanning electron microcopy images revealed that all types of hNPs were approximately spher- ical and porous with average diameter 1?5 􏰅m, and smaller than CaCO3 microparticles. The presence of biopolymers in the matrices was confirmed after derivatization with a fluorescein isothiocyanate probe by means of confocal microscopy and FTIR synchrotron beamline analysis. In addition, the coupling of lambda carrageenan (􏰎-Car) to FA in the microparticles (FA?􏰎-Car-hNPs) increased the cancer-cell tar- geting and also extended the specific surface area by up to ninefold (26.6m2 g−1), as determined by the Brunauer?Emmett?Teller isotherm. A nanostructured porous surface was found in all instances, and the FA?􏰎-Car-hNP pore size was about 30 nm, as calculated by means of the Barrett?Joyner?Halenda adsorption average. The test of FA?􏰎-Car-hNP anticancer activity on human osteosarcoma MG-63 cell line showed cell viabilities of 13% and 100% with and without Dox, respectively, as determined by crystal violet staining after 24 h of incubation.