Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles

Carboxymethyl cellulose (CMC)-doped CaCO3 microparticles with an average diameter of 5 mu m were prepared and coated by chitosan and alginate multilayers. The prepared CaCO3 microparticles had a dominant phase of vaterite and a spherical morphology with nanopores on their surface. After LbL assembly of chitosan and alginate, the CaCO3 microparticles were significantly smoothened. Treatment of the multilayers-coated particles yielded hollow microcapsules. These particles could spontaneously load positively charged doxorubicin (DOX) molecules, whose amount was 475 and 482 mg DOX/g CaCO3 for the CaCO3(CMC) microparticles and the (chitosan/alginate)(5) coated CaCO3(CMC) microparticles, respectively. Brunauer-Emmett-Teller (BET) method was used to analyze the specific surface area and the pore size distribution of the CaCO3(CMC) microparticles before and after DOX loading. After DOX loading, S-BET and pore volume were reduced obviously, and the volume of smaller pores decreased significantly, whereas that of larger pores were increased. The increase of the volume of larger pores was explained by an electric charge screening effect. DOX release from the CaCO3 microparticles in pH 5 was relatively slow within the first 15 h, and could be sustained to more than 150 h. The release amount at lower pH was larger at the same time. Coating of the CaCO3(CMC) microparticles with the chitosan/alginate multilayers could obviously assuage the initial burst release and reduce the release rate. (C) 2009 Elsevier B.V. All rights reserved.