Development of the new pH-driven carrier from alginate/carboxymethyl starch bio-coated co-drugs@COF-OH for controlled and concomitant colon cancer treatment

Int J Biol Macromol. 2023 Jun 1:239:124322. doi: 10.1016/j.ijbiomac.2023.124322. Epub 2023 Apr 3.

Abstract

To develop a new more efficient colon cancer treatment bio-vehicle, in frontier research, for the first time, an attempt has been made to design a unique colon-targeted bio-carrier containing polysaccharides along with nanoporous materials. So, at first, an imine-based covalent organic framework (COF-OH) with respectively an average pore diameter and surface area at 8.5058 nm and 208.29 m2·g-1 was fabricated. In the next step, about 41.68 % and 95.8 % of 5-fluorouracil (5-Fu) and curcumin (CUR) respectively were loaded on COF-OH, and 5-Fu + CUR@COF-OH was achieved. Due to the higher rate of drug releases in simulated stomach media, 5-Fu + CUR@COF-OH was coated with a mixture of alginate (Alg) and carboxymethyl starch (CMS) via the ionic crosslinking (Alg/CMS@(5-Fu + CUR@COF-OH)). Findings displayed that the use of polysaccharide coat reduce the drug releases in simulated gastric and improved it in simulated intestinal and colonic fluids. The beads swelled about 93.33 % under simulated gastrointestinal conditions, but this value was found higher in the simulated colonic environment and reached 326.67 %. The hemolysis rate lower than 5 %, as well as the cell viability higher than 80 %, were the main showing signs of system biocompatibility. Altogether, the results of the preliminary investigations can highlight the potential of the Alg/CMS@(5-Fu + CUR@COF-OH) for colon-specific drug delivery.

Keywords: 5-Fluorouracil; Alginate/carboxymethyl starch bead; Colon cancer; Curcumin; Oral drug delivery; pH-sensitivity.

MeSH terms

  • Alginates / therapeutic use
  • Colonic Neoplasms* / drug therapy
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Drug Carriers / therapeutic use
  • Excipients
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Hydrogen-Ion Concentration
  • Metal-Organic Frameworks*
  • Pharmaceutical Preparations

Substances

  • Metal-Organic Frameworks
  • carboxymethyl starch
  • Alginates
  • Fluorouracil
  • Curcumin
  • Pharmaceutical Preparations
  • Excipients
  • Drug Carriers