Ternary nanocomposite carriers based on organic clay-lipid vesicles as an effective colon-targeted drug delivery system: preparation and in vitro/in vivo characterization

Abstract

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit ® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit ® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit ® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model

“…This indicates that the absorption mechanism of the liposomes is related to the phagocytic property of macrophages [46]. Furthermore, a previous study of nanocomposite carriers using aminoclay and Eudragit in LPS-stimulated RAW 264.7 cells, found no toxicity to macrophages [45]. The results of these publications, taken together with those of the current study, indicate that these nanocomposites may be good candidates as carriers for oral drug delivery.…”

“…In this study, we orally administered IFX targeting the colon using liposomes, aminoclay, and Eudragit S100-based nanocomposite carriers. In previous studies, in vivo image analysis by confocal microscopy confirmed the effective intracellular distribution of fluorescently labeled nanocomposite carriers in the colon [44,45]. The expression of each macrophage marker gene and the accumulation of liposomes showed a significant positive correlation, and liposomes enhanced the accumulation of drug candidates through macrophages in damaged colon tissues [46].…”

“…The 3-aminopropyl-functionalized magnesium phyllosilicate (aminoclay) was synthesized by following a method described previously [45]. Before coating, the bulk aminoclay powder was dispersed in water, followed by ultrasonication for 10 min, for the exfoliation of the aminoclay.…”

Nanocomposites-Based Targeted Oral Drug Delivery Systems with Infliximab in a Murine Colitis Model

“…In this study, we orally administered IFX targeting the colon using liposomes, aminoclay, and Eudragit S100-based nanocomposite carriers. In previous studies, in vivo image analysis by confocal microscopy con rmed the effective intracellular distribution of uorescently labeled nanocomposite carriers in the colon [44,45]. The expression of each macrophage marker gene and the accumulation of liposomes showed a signi cant positive correlation, and liposomes enhanced the accumulation of drug candidates through macrophages in damaged colon tissues [46].…”

Nanocomposites-Based Targeted Oral Drug Delivery Systems with Infliximab in a Murine Colitis Model

“…In this study, we orally administered IFX targeting the colon using liposomes, aminoclay, and Eudragit S100-based nanocomposite carriers. In previous studies, in vivo image analysis by confocal microscopy con rmed the effective intracellular distribution of uorescently labeled nanocomposite carriers in the colon [38,39]. The expression of each macrophage marker gene and the accumulation of liposomes showed a signi cant positive correlation, and liposomes enhanced the accumulation of drug candidates through macrophages in damaged colon tissues [40].…”