Synthetic Calcium Silicate Biocomposite Based on Sea Urchin Skeleton for 5-Fluorouracil Cancer Delivery

Abstract

Synthetic calcium silicates and phosphates are promising compounds for targeted drug delivery for the effective treatment of cancerous tumors, and for minimizing toxic effects on the patient's entire body. This work presents an original synthesis of a composite based on crystalline wollastonite CaSiO₃ and combeite Na₄Ca₄(Si₆O₁₈), using a sea urchin Mesocentrotus nudus skeleton by microwave heating under hydrothermal conditions. The phase and elemental composition and structure of the obtained composite were studied by XRF, REM, BET, and EDS methods, depending on the microwave heating time of 30 or 60 min, respectively, and the influence of thermo-oxidative post-treatment of samples. The role of the sea urchin skeleton in the synthesis was shown. First, it provides a raw material base (source of Ca²⁺) for the formation of the calcium silicate composite. Second, it is a matrix for the formation of its porous inorganic framework. The sorption capacity of the composite, with respect to 5-fluorouracil, was estimated, the value of which was 12.3 mg/L. The resulting composite is a promising carrier for the targeted delivery of chemotherapeutic drugs. The mechanism of drug release from an inorganic natural matrix was also evaluated by fitting its release profile to various mathematical models.

Keywords: calcium silicate; drug delivery system; hydrothermal synthesis; microwave synthesis; sea urchin skeleton; wollastonite.

Figure 1

X-ray patterns of material samples obtained from the sea urchin skeleton: (1) initial sea urchin skeleton calcined at 800 °C in the air; (2) sample after 30 min microwave treatment; (3) sample after 60 min microwave treatment; (4) sample (2) after additional 800 °C thermal oxidation treatment; (5) sample (3) after additional 800 °C thermal oxidation treatment.

Figure 2

XRD comparisons of 180 °C experimental sample with reference structures: (1) Na4Ca4Si6O18 phases; (2) sample after 30 min microwave treatment after additional 800 °C thermal oxidation treatment.

Figure 3

Low-temperature nitrogen sorption-desorption isotherms (a) and DFT-calculated pore size distribution histograms (a*) for the sample material obtained after the microwave and thermal oxidation treatments.

Figure 4

SEM images of the samples: (a–a**) original sea urchin skeleton; (b–b**) original sea urchin skeleton, calcined at 800 °C in air; (c–c**) sample after 30 min microwave synthesis; (d–d**) sample after 60 min microwave synthesis; (e–d**, f–e**) samples obtained by microwave synthesis after additional thermal oxidation treatment at 800 °C.

Figure 5

EDS analysis of the samples: (a) original sea urchin skeleton, calcined at 800 °C in the air; (b) sample after 30 min microwave treatment; (c) sample after 60 min microwave treatment; (d,e) samples obtained by microwave synthesis after additional thermal oxidation treatment at 800 °C.

Figure 6

Light absorption spectra of the calibration solutions, and of the solution in the presence of the synthesized calcium silicate composite material at different pH ((a)—pH = 3, (b)—pH = 7, (c)—pH = 10), specially added table to study sorption values of 5-FU in more detail.

Figure 7

Ionization of the 5-fluorouracil molecule.

Figure 8

Analysis of drug release kinetics. (a–a**)—application of the Baker-Lonsdale model to both stages of the 5-fluorouracil release profile; (b–b**)—application of the Hixson-Crowell model to both stages of the 5-fluorouracil release profile; (c–c**)—application of the first-order model to both stages of the 5-fluorouracil release profile; (d–d**)—application of the Higuchi model to both stages of the 5-fluorouracil release profile.

Figure 9

Calcium degradation from the inorganic matrix (a) and percentage of 5-fluorouracil leached from the inorganic matrix (b).