Novel Drug Carrier: 5-Fluorouracil Formulation in Nanoporous Biogenic Mg-calcite from Blue Crab Shells-Proof of Concept

Geza Lazar; Fran Nekvapil; Razvan Hirian; Branko Glamuzina; Tudor Tamas; Lucian Barbu-Tudoran; Simona Cinta Pinzaru

doi:10.1021/acsomega.1c03285

Novel Drug Carrier: 5-Fluorouracil Formulation in Nanoporous Biogenic Mg-calcite from Blue Crab Shells-Proof of Concept

ACS Omega. 2021 Oct 11;6(42):27781-27790. doi: 10.1021/acsomega.1c03285. eCollection 2021 Oct 26.

Authors

Geza Lazar^{1

2}, Fran Nekvapil^{1

2}, Razvan Hirian³, Branko Glamuzina⁴, Tudor Tamas⁵, Lucian Barbu-Tudoran^{6

7}, Simona Cinta Pinzaru^{1

2}

Affiliations

¹ Biomolecular Physics Department, Babes Bolyai University, Kogalniceanu 1, RO-400084 Cluj-Napoca, Romania.
² Institute for Research, Development and Innovation in Applied Natural Science, Fântânele 30, 400327 Cluj-Napoca, Romania.
³ Babes Bolyai University, Faculty of Physics, Kogalniceanu 1, RO-400084 Cluj-Napoca, Romania.
⁴ Department of Aquaculture, University of Dubrovnik, Ćira Carića 4, 20 000 Dubrovnik, Croatia.
⁵ Department of Geology, Babeş-Bolyai University, Kogălniceanu 1, RO-400084 Cluj-Napoca, Romania.
⁶ Electron Microscopy Centre, Babes;-Bolyai University, Clinicilor 5-7, 400006 Cluj-Napoca, Romania.
⁷ Advanced Research and Technology Center for Alternative Energy, National Institute for Research and Development of Isotopic and Molecular Technologies, Donat 67-103, 400293 Cluj-Napoca, Romania.

Abstract

The ever-growing demand for novel, cheaper, and more effective drugs has put nanomedicine and targeted drug delivery to the forefront of scientific innovation. Owing to its porous three-dimensional (3D)-nanostructure and properties, the biogenic calcite from wasted blue crab shells is employed in the present work as a new drug carrier for 5-fluorouracil (5-FU), a drug widely used in cancer therapy. The drug solution has been loaded in the porous nanoarchitecture of the powdered biogenic material and further pelleted in tablets with a 5-FU concentration of 1.748 mg/g. Their structural and morphological properties were characterized using Raman, X-ray diffraction, and scanning electron microscopy. Confocal micro-Raman spectra of tablet surface showed a typical signal of biogenic carbonate with preserved carotenoids and carotenoproteins found in the native waste shell, while the drug Raman signal was absent, indicating its adsorption in the intricate nanoporous biogenic carrier. The slow release of the drug from the newly formulated tablet was investigated by tracking the surface-enhanced Raman scattering (SERS) signal of the tablet solution in a series of time-dependent experiments. The SERS signal quantification is achieved using the well-known SERS spectral fingerprint of 5-fluorouracil aqueous solution adsorbed on Ag nanoparticles. The proof of concept is demonstrated by quantifying the slow release of the drug through the characteristic SERS band intensity of 5-FU in a time course of 26 h. This proof of concept boosted further investigations concerning the released drug identity in simulated solutions that mimic the pH of the upper- and lower gastrointestinal tract, as well as the multiple possibilities to control porosity and composition during powdering and treatment of biogenic material, to achieve the most convenient formulation for relevant biomedical drug delivery. Nonetheless, the present results showed great promise for innovative reusing waste biogenic 3D-nanomaterials of aquatic origin as advantageous drug carriers for slow release purposes, in line with the concept of blue bioeconomy.