Correction: Bioreducible and acid-labile polydiethylenetriamines with sequential degradability for efficient transgelin-2 siRNA delivery.

Correction for 'Bioreducible and acid-labile polydiethylenetriamines with sequential degradability for efficient transgelin-2 siRNA delivery' by Pengchong Wang et al., J. Mater. Chem. B, 2019, 7, 6994-7005, https://doi.org/10.1039/C9TB01183H.

Mucoadhesive nanoparticles-based oral drug delivery systems enhance ameliorative effects of low molecular weight heparin on experimental colitis.

Low molecular weight heparin (LMWH) is reported to have therapeutic action on ulcerative colitis (UC). To facilitate its oral administration and improve the colon-targeting property, LMWH-loaded nanoparticles (TMC-NPs and SA-TMC-NPs) are prepared and evaluated by a series of studies, including their stabilities, drug release profiles, mucosal permeation, mucoadhesion, cytotoxicities, cellular uptake profiles, anticoagulant and anti-inflammatory activities, mucosal healing properties, biosafety and ameliorative effects on experimental colitis. Consequently, oral administration of LMWH-loaded NPs for 5 days perform significant therapeutic effects on mice, which are manifested as improved body weight gains, colon length, DAI score, MPO activity and histological characteristics. Besides, SA-TMC-NPs show better colon-targeting property than TMC-NPs that is demonstrated by lower oral absorption (ATPP 38.95 s) and stronger mucoadhesion (kcps reduces 36.46 %) to inflamed colon tissues. Therefore, TMC-based NPs are proved to be as promising oral colon-targeting drug delivery systems of LMWH and has potential application in UC treatment.

Bioreducible and acid-labile polydiethylenetriamines with sequential degradability for efficient transgelin-2 siRNA delivery.

The transgelin-2 (TAGLN2) protein plays an important role in multidrug resistance in human breast cancer. siRNA mediated gene silencing of TAGLN2 is a promising strategy for paclitaxel resistance reversal in breast cancer. In this study, a series of bioreducible and acid-labile polydiethylenetriamines (PDs) with different proportions of cross-linkers were synthesized. TAGLN2 siRNA was condensed by PDs to form dual-responsive nanocomplexes, and these nanocomplexes were hypothesized to partially degrade in the acidic environment of endosomes, and then completely degrade in the reducing environment of the cytoplasm to release siRNA. It was found that PDs have good water solubility, acid-base buffering capacity, suitable degradability and high biocompatibility. Moreover, PDCKM can deliver TAGLN2 siRNA into MCF-7/PTX cells and inhibit the expression of TAGLN2 even better than PEI 25k. Besides, paclitaxel showed higher cytotoxicity in cells incubated with PDCKM/TAGLN2 siRNA nanocomplexes. These results suggested that PDs have great potential for safe and efficient siRNA delivery to reverse paclitaxel resistance in breast cancer.

Synthesis of budesonide conjugates and their anti-inflammatory effects: a preliminary study.

PURPOSE: Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility. MATERIALS AND METHODS: Seven novel Bud conjugates (3a-3g) were designed and synthesized in this study. Besides, the equilibrium solubility, cell viability, in vitro and in vivo anti-inflammatory activity, and the hydrolysis behavior of the conjugates in different pH solutions, rat and human plasma, and rat lung homogenate were studied in detail. RESULTS: As compared to Bud, the equilibrium solubility of 3a, 3c, and 3e was significantly increased; 3a, 3b, and 3c significantly inhibited the interleukin-6 production in lipopolysaccharide-induced A549 cells; 3a and 3e could significantly decrease the xylene-induced ear edema; and 3a and 3c were gradually and slowly hydrolyzed into Bud in the alveolar fluid and lung homogenate and broken down quickly in plasma. CONCLUSION: The amino acid ester compounds budesonide-21-glycine ester (3a) and budesonide-21-alanine ester (3c) were selected as potential conjugates of Bud. This study would provide a theoretical and an experimental basis for the in vivo process of glucocorticoids and the treatment of inflammatory diseases.

Pulvis Fellis Suis extract attenuates ovalbumin-induced airway inflammation in murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulvis Fellis Suis (PFS), named with "Zhu Danfen" in China, has been extensively used for the therapy of enteritis, acute pharyngitis, whooping cough and asthma in folk medicine. Although PFS shows anti-inflammatory activities, its effect on airway inflammation in asthma has not been studied. AIM OF THE STUDY: To explore the protective effect of PFS ethanol extract against airway inflammation in asthmatic mice. MATERIALS AND METHODS: Allergic asthma in mice was sensitized and challenged by OVA. Mice were administered in oral with PFS daily at doses of 100, 200 and 400mg/kg on days 21-27. Inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were analyzed. Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) and periodic acid-schiff (PAS) staining. The IgE level in serum was measured by using enzyme-linked immunoassay (ELISA). ELISA was also used to detect the levels of Th1/Th2 cytokine and eotaxin in BALF. RESULTS: Histological results revealed that PFS could ameliorate OVA-induced histological changes by attenuating inflammatory cell infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. Treatment with different doses of PFS significantly decreased the elevated inflammatory cell numbers in BALF and IgE production in serum. PFS treatment reduced the production of Th2 cytokine IL-4, IL-5, IL-13, and promoted Th1 cytokine IFN-γ production in BALF. In addition, PFS also decreased the levels of eotaxin and TNF-α in BALF. CONCLUSIONS: These findings suggest that PFS has a markedly anti-inflammatory effect on OVA-induced allergic asthma in mice, and could be a promising protective agent recommended for allergic asthma patients.

Intestinal anti-inflammatory effect of the rhizome extracts of Menispermum dauricum DC. on trinitrobenzene sulfonic acid induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Menispermum dauricum DC., commonly known as "Bei Dou Gen" (BDG) in China, has been used extensively in folk medicine to treat inflammatory diseases, especially intestinal inflammations such as enteritis and dysentery, and in pharyngitis, tonsillitis, rheumatism and bronchitis. Although previous studies showed that BDG has anti-inflammatory activities, its effects on ulcerative colitis (UC) have not yet been explored. AIM OF THE STUDY: To investigate the intestinal anti-inflammatory effect of the rhizome extracts of Menispermum dauricum DC. on UC model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. MATERIALS AND METHODS: UC in mice was induced by colonic administration with TNBS. BDG (100, 200 and 400mg/kg/day) and sulfasalazine (500mg/kg/day) were administered orally for 7 consecutive days. The inflammatory degree was assessed by gross appearance, macroscopic and histological analysis, and accumulation of myeloperoxidase (MPO) activity. Pro-inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, were determined by enzyme-linked immunoassay. The expression of cyclooxygenase (COX)-2 was assessed by immunohistochemical analysis. RESULTS: Treatment with different doses of BDG significantly ameliorated macroscopic damage and histological changes, reduced the accumulation of MPO activity, depressed serum and colonic tissue levels of TNF-α, IL-1ß and IL-6 in a dose-dependent manner. In addition, administration of BDG effectively reduced COX-2 overexpression in colon. CONCLUSION: We demonstrated for the first time that BDG possessed marked intestinal anti-inflammatory effect in TNBS induced colitis in mice, which might be related to the reduction of up-regulated productions and expressions of pro-inflammatory mediators, suggesting that it may have beneficial use for the treatment of inflammatory bowel disease.

Anti-inflammatory effect of taurocholate on TNBS-induced ulcerative colitis in mice.

Taurocholate is a natural conjugated bile acid. The aim of this study was to evaluate the anti-inflammatory effect of taurocholate in TNBS-induced ulcerative colitis in mice. The colitis were induced by rectal administration of TNBS. After 24h, the experimental animals were treated with sulfasalazine (SASP, 500mg/kg/day) and taurocholate (20, 40 and 60mg/kg) for 7 consecutive days. The anti-inflammatory effects of taurocholate for colitis were assessed by body weight, colonic weight and length, macroscopic scores, and histopathological examinations. In addition, the colonic tissue levels of myeloperoxidase (MPO) activity, interleukin (IL)-1ß, interferon (IFN-γ) and tumour necrosis factor-α (TNF-α) were also determined to assess the effect of taurocholate. Compared with the model group, treatment with taurocholate (20, 40 and 60mg/kg) significantly inhibited the body weight loss, improved colonic weight and length, and decreased macroscopic and histopathological scores. Furthermore, the activity accumulation of MPO and the colonic tissue levels of IL-1ß, IFN-γ and TNF-α were also decreased by administration of taurocholate. All the findings of this study suggested that taurocholate has the anti-inflammatory effect in ulcerative colitis in mice and indicated it as a good candidate to treat inflammatory bowel disease.

Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice.

Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60mg/kg) and sulfasalazine (500mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1ß, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1ß, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice.