Delivery of Berberine Using Chitosan/Fucoidan-Taurine Conjugate Nanoparticles for Treatment of Defective Intestinal Epithelial Tight Junction Barrier

Abstract

Bacterial-derived lipopolysaccharides (LPS) can cause defective intestinal barrier function and play an important role in the development of inflammatory bowel disease. In this study, a nanocarrier based on chitosan and fucoidan was developed for oral delivery of berberine (Ber). A sulfonated fucoidan, fucoidan-taurine (FD-Tau) conjugate, was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy. The FD-Tau conjugate was self-assembled with berberine and chitosan (CS) to form Ber-loaded CS/FD-Tau complex nanoparticles with high drug loading efficiency. Berberine release from the nanoparticles had fast release in simulated intestinal fluid (SIF, pH 7.4), while the release was slow in simulated gastric fluid (SGF, pH 2.0). The effect of the berberine-loaded nanoparticles in protecting intestinal tight-junction barrier function against nitric oxide and inflammatory cytokines released from LPS-stimulated macrophage was evaluated by determining the transepithelial electrical resistance (TEER) and paracellular permeability of a model macromolecule fluorescein isothiocyanate-dextran (FITC-dextran) in a Caco-2 cells/RAW264.7 cells co-culture system. Inhibition of redistribution of tight junction ZO-1 protein by the nanoparticles was visualized using confocal laser scanning microscopy (CLSM). The results suggest that the nanoparticles may be useful for local delivery of berberine to ameliorate LPS-induced intestinal epithelia tight junction disruption, and that the released berberine can restore barrier function in inflammatory and injured intestinal epithelial.

Marine Polysaccharides in Pharmaceutical Applications: Fucoidan and Chitosan as Key Players in the Drug Delivery Match Field

“…The most commonly used preparation strategy is complexation by employing a simple polyelectrolyte self-assemble method initially described by Lee et al [109]. In this procedure, it is possible to combine different weight ratios by mixing solutions of chitosan to solutions of fucoidan, and then the mixture is sonicated at room temperature [110][111][112][113][114]. According to the literature, with this method, it is possible to obtain nanoparticles of 100-300 nm with approximately 90% encapsulation efficiency.…”

“…However, the pH-responsive profile of fucoidan-chitosan nanoparticles prevents degradation under acidic conditions of the gastrointestinal tract and allows drug absorption in the intestine. Hence, fucoidan-chitosan nanoparticles have been widely explored for oral delivery of active pharmaceutical ingredients [110,111,113,118,[123][124][125][126][127][128][129], also taking advantage of chitosan's property of increased contact with the mucus layer and consequently longer resistance times at the absorption site [129]. The biological properties of fucoidan described in Section 3.1.1 were explored by some authors to obtain synergic effects with a drug, for example, ciprofloxacin [117] or gemcitabine [126].…”

“…Moreover, the benefits of fucoidan-chitosan nanoparticles in polyphenols delivery by improving aqueous solubility and, consequently, oral bioavailability, led also to the development of nanostructures for the delivery of berberine, red ginseng, and quercetin [113,127,131]. Generally, these nanoparticles demonstrated their ability to control polyphenols release, retain biological activity, and prevent degradation.…”

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

“…16 Besides, oral administration, especially at a high dose, often causes gastrointestinal discomfort due to considerable exposure to free berberine. 17 Therefore, it is necessary to develop advanced formulations of berberine to improve the oral delivery efficacy, thereby enhancing the in vivo antidiabetic effect.…”

Pharmacological, pharmaceutical, cosmetic and diagnostic applications of sulfated polysaccharides from marine algae and bacteria

“…Self-assembly of sulfonated fucoidan, fucoidan-tauran with berberine and chitosan resulted in the formation of nanoparticles with high loading efficiency and fast release in simulated intestinal fluid. Thus they can be used in the local delivery of berberine for treatment of defective intestinal tight junction barrier (Wu et al, 2014).…”