Search

Abstract: The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200mg/kg) was administered for 14days, 1day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E2 (PGE2) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (IκBα) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE2, as well as the expressions of iNOS, COX-2 and NF-κB p65 proteins in the colonic mucosa, and the significant decrease in expressions of IκBα proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100mg/kg and 200mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the IκBα/NF-κB p65 expression. [Copyright &y& Elsevier]

Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physiological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Context: As a glucocorticoid drug, dexamethasone has good therapeutic effects for ulcerative colitis. pH-sensitive hydrogels could make conventional changes of volume in response with different pH values. Meanwhile, they could load drugs depending on its internal three-dimensional network structure. Objective: Appropriate methods were used to improve the drug-loading capacity of hydrogel and exploring the colon-targeting character of dexamethasone hydrogel. Materials and methods: Different solvents (ethanol and 1,2-propanediol) were employed to dissolve dexamethasone as well as hydrogel monomer materials (poly(ethylene glycol) methyl ether (MPEG)–poly(lactide acid)–acryloyl chloride macromonomer, itaconic acid (IA) and MPEG–methacrylate), then mixing them together to prepare hydrogel through the heat-initiated free radical polymerization method. Differential scanning calorimetry and X-ray diffraction methods were used to verify whether dexamethasone was loaded into hydrogels.In vitrodrug release behavior andin vivopharmacokinetic study were also investigated in detail. Results: Dexamethasone was successfully loaded into hydrogel, and its loading capacity was improved (5 mg/g). Both thein vitrorelease study and thein vivopharmacokinetic study showed the good colon-targeting character of the pH-sensitive P(LE–IA–MEG) hydrogel (Tmax = 1.0 h, Cmax = 2.16 µg/ml of dexamethasone; Tmax = 3.9 h, Cmax = 0.43 µg/ml of dexamethasone hydrogel). Discussion: Dexamethasone could be targeted to the colon site by P(LE–IA–MEG) hydrogel, thereby improving its therapeutic effect and reduce its side effects. Conclusion: P(LE–IA–MEG) hydrogel might have great potential application in colon-targeted drug delivery systems. [ABSTRACT FROM AUTHOR]

In our previous study, we synthesized a pH-sensitive hydrogel based on poly (ɛ-caprolactone) (PCL), Pluronic (Poloxamer) and methacrylic acid (MAA) using UV-initiated free-radical polymerization. In the present study, we evaluated the safety of the obtained GMA–PCFC–GMA copolymer and a P(CFC–MAA–MEG) hydrogel both in vitro and in vivo . The pharmacokinetics study and distribution characteristics of dexamethasone in rat blood and mouse colon were investigated in detail. The in vitro toxicity of the GMA–PCFC–GMA copolymer was evaluated using a cell viability assay with HEK293 cells. An acute oral toxicity test was conducted by orally administering mice with a total of 10,000 mg/kg body weight of the P(CFC–MAA–MEG) hydrogel. The mice were then observed continuously for 14 days. After which, they were sacrificed and their blood collected for routine blood and serum chemistry tests. Pharmacokinetic and colonic tissue distribution studies were conducted using high-performance liquid chromatography to detect the concentration of dexamethasone in rat blood and mouse colon tissue. All of the results indicated that both the GMA–PCFC–GMA copolymer and P(CFC–MAA–MEG) hydrogel were nontoxic. Moreover, the hydrogel significantly enhanced the colon-targeting behavior of dexamethasone. These results suggested that the novel hydrogel has great potential in colon-targeted drug delivery. [ABSTRACT FROM AUTHOR]

A series of biodegradable and pH/thermosensitive hydrogels based on monomethoxyl poly(ethylene glycol) (MPEG), poly(ϵ-caprolactone) (PCL), methylacrylic acid (MAA), and N-Isopropylacrylamide (NIPAAm) were prepared by UV-initiated free radical polymerization method. Swelling behavior and hydrolytic degradable behavior in aqueous medium with different pH values and pH/thermosensitivity of the hydrogels were studied in detail. The prepared biodegradable pH/thermo-sensitive hydrogels based on PCL, MPEG, MAA, and NIPAAm may have great potential application in smart drug delivery system. [ABSTRACT FROM PUBLISHER]

Targeting drug system (TDS) or targeted drug delivery system (TDDS) is a new kind of drug delivery system which could make drug to be directly concentrated on the target site with high curative effects and low side-effects. As the quintessence of Chinese culture, traditional Chinese medicine (TCM) has a large advantage in many disease clinical treatments, especially in cancer, hypertension and many other intractable diseases owing to their low toxicity and side-effects relative to western medicine. This article reviews literatures on development of TCM-targeted preparations which were published in the past 10 years. TDS including active-targeting, passive-targeting and physical-chemical-targeting preparations were introduced through domestic and overseas literatures to reveal the unique advantages of TCM-targeting preparations in drug delivery system. In this article, we have reviewed some kinds of TCM-targeting preparations and indicated that great attention should be paid to the research on the TCM-targeting preparations. [ABSTRACT FROM AUTHOR]