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Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors

Authors Kolmas J, Pajor K, Pajchel L, Przekora A, Ginalska G, Oledzka E, Sobczak M

Received 2 May 2017

Accepted for publication 2 June 2017

Published 7 August 2017 Volume 2017:12 Pages 5633—5642


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

Joanna Kolmas,1 Kamil Pajor,1 Lukasz Pajchel,1 Agata Przekora,2 Grażyna Ginalska,2 Ewa Oledzka,3 Marcin Sobczak3

1Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with Laboratory Medicine Division, Medical University of Warsaw, Warsaw, 2Department of Biochemistry and Biotechnology, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Lublin, 3Department of Biomaterials Chemistry, Faculty of Pharmacy with Laboratory Medicine Division, Medical University of Warsaw, Warsaw, Poland

Abstract: Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1–1.5 mm in 2 ways: during the granules’ preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13C and 31P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a “burst release” probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals’ interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the “burst release” of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well.

Keywords: composites, nanocrystalline hydroxyapatite, drug release, cytotoxicity, antitumor activity, ionic substitutions, biomaterials, bisphosphonates

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