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

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.

Rapid and Application-Tailored Assessment Tool for Biogenic Powders from Crustacean Shell Waste: Fourier Transform-Infrared Spectroscopy Complemented with X-ray Diffraction, Scanning Electron Microscopy, and Nuclear Magnetic Resonance Spectroscopy

“…The proposed FTIR method can be easily used to evaluate the chemical composition of the waste biomaterial, which is in turn useful for decision-making regarding the development of advanced applications of biogenic powders such as pharmaceutical carriers, loaded powders with various fluids for new composite materials, adsorbents for environmental decontamination, and many others. Although this method cannot differentiate between crab species, it may be successfully applied in evaluating other categories of biogenic materials from seafood waste, such as oysters, snails, urchin shells, and shrimps, all consisting of calcite or calcite/aragonite, as main minerals and various amounts of organic materials.…”

pH-Dependent Behavior of Novel 5-FU Delivery System in Environmental Conditions Comparable to the Gastro-Intestinal Tract

“…The preparation of the biogenic shell powder is described in detail in our previous studies [ 26 , 27 , 28 ], and the same procedure was followed in the present paper.…”

“…In our previous work [ 26 ], we successfully developed a novel pharmaceutical formulation of 5-FU based on an abundant yet largely unused biomaterial, the wasted shells of the Atlantic Blue Crab ( Callinectes sapidus ). The biogenic waste material was chosen as drug carrier for 5-FU based on its remarkable physico-chemical properties, preparation method, and availability and biocompatibility, which confer considerable advantages over other drug delivery systems.…”

“…We previously conducted comprehensive analyses on the biogenic powders result33ing from crustacean shells [ 26 , 27 , 28 ]. Confocal Raman micro-spectroscopy (CRM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) method [ 31 ], and X-ray diffraction (XRD) were used to investigate the morphology and composition of the blue crab shell powder pre [ 27 , 28 ] and post drug loading with pelleting into tablets [ 26 ], demonstrating the adsorption of the drug (5-FU) in the pores of the biogenic carrier [ 26 ].…”

“…We previously conducted comprehensive analyses on the biogenic powders result33ing from crustacean shells [ 26 , 27 , 28 ]. Confocal Raman micro-spectroscopy (CRM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) method [ 31 ], and X-ray diffraction (XRD) were used to investigate the morphology and composition of the blue crab shell powder pre [ 27 , 28 ] and post drug loading with pelleting into tablets [ 26 ], demonstrating the adsorption of the drug (5-FU) in the pores of the biogenic carrier [ 26 ]. Moreover, surface enhanced Raman scattering (SERS) was employed as a novel highly sensitive and specific method to monitor the slow release of the active ingredient (5-FU) from the newly formulated tablets suspended in water, thus quantifying the amount of drug released from the tablet and proving the concept and viability of the newly formulated composite drug [ 26 ].…”