Preparation and characterization of cross-linked microspheres C(Dex-g-PSSS) and their drug-carrying and colon-specific drug delivery properties

Abstract

The graft polymer Dex-g-PSSS was obtained through poly(sodium 4-styrene sulfonate) (PSSS) grafted on dextran(Dex) by using the cerium salt-hydroxyl group redox initiation system. The cross-linked microspheres C(Dex-g-PSSS) were synthesized by suspension polymerization with epichlorohydrin as the cross-linking agent. The chemical structure and physicochemical characteristics of C(Dex-g-PSSS) microspheres were represented by infrared spectroscopy (FTIR), optical microscope, and zeta potential analysis. The aim of the study is to constitute a colon-specific drug delivery system via molecular design, using C(Dex-g-PSSS) microspheres as the drug-carrying material and taking 5-fluorouracil (5-FU) as the model drug. The drug-carrying ability and mechanism of the cross-linked microspheres C(Dex-g-PSSS) for 5-FU were investigated. Finally, in vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in the medium with pH 2, the cross-linked microspheres C(Dex-g-PSSS) exhibit a strong adsorption ability for 5-FU because of strong electrostatic interactions and have an adsorption capacity of 154 ± 7.5 mg/g, displaying high drug-carrying efficiency. The in vitro release behavior of the drug-carrying microspheres is highly dependent on pH and dextranase. In the medium with pH 2, the drug-carrying microspheres do not release the drug and in the medium with pH 1, they release a little, whereas in the medium with pH 7.4, a sudden delivery phenomenon of the drug will occur, and in the presence of dextranase, a more sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior.

Design and application of oral colon administration system

“…In the study of pH-enzyme triggered colon-targeted drug delivery system, dextran was used as matrix material to prepare cross-linked microspheres C (Dex-g-PSSS) by graft polymerization and inverse emulsification cross-linking technology 56 , 57 . Under the condition of pH = 2, the gelled microspheres with double control of enzymes and pH had strong adsorptive power to 5-fluorouracil, and hardly release the drug.…”

Redox-Responsive Nanophotosensitizer Composed of Chlorin e6-Conjugated Dextran for Photodynamic Treatment of Colon Cancer Cells

“…Swelling ratio of dextran hydrogel was increased 45 times in the presence of dextranase and 5-aminosalicylic acid release was also increased by degradation of dextran linkage as discussed by Kim and Oh [34]. Jianping et al synthesized poly(sodium 4-styrene sulfonate)-grafted dextran and fabricated pH-/enzyme-sensitive microspheres for 5-fluorouracil delivery to the colon [32]. They argued that microspheres released the drug a little in the pH 7.4 and sudden delivery phenomenon of the drug occurred in the presence of dextranase while they did not release the drug in the acidic pH environment.…”

“…Since dextran can be degraded by dextranase in the colonic region, various polymeric conjugates, nanoparticles, and microspheres have been investigated using dextran [30][31][32][33][34][35]. Swelling ratio of dextran hydrogel was increased 45 times in the presence of dextranase and 5-aminosalicylic acid release was also increased by degradation of dextran linkage as discussed by Kim and Oh [34].…”