Development of bifunctional colon-specific delivery system of prednisolone using chitosan capsules and inhibitors of efflux transporters

在这项研究中，我们考察了壳聚糖胶囊在大鼠结肠定位释放强的松龙的有效性。并与常规剂型(明胶胶囊)比较，评价壳聚糖胶囊与常规剂型(明胶胶囊)治疗强的松龙的疗效和不良反应。与明胶胶囊相比，壳聚糖胶囊口服泼尼松龙后，大鼠大肠粘膜中强的松龙浓度显著增加。而口服壳聚糖胶囊后的强的松龙血药浓度明显低于明胶胶囊。我们还通过测定线粒体过氧化物酶(MPO)活性和结肠湿重/体重(C/B)比率来评价强的松龙对三硝基苯磺酸(TNBS)诱导的结肠炎愈合的疗效。与明胶胶囊相比，用壳聚糖胶囊口服强的松龙后，MPO活性和C/B比值显著降低。此外，用明胶胶囊口服强的松龙后，胸腺重量明显减少，而用壳聚糖胶囊口服强的松龙后，胸腺重量变化不大。这些结果表明，壳聚糖胶囊可能有助于强的松龙的结肠定位释放，并增强其对结肠炎的愈合作用。此外，壳聚糖胶囊还可能有效地减少强的松龙的副作用，因为它减少了肠道对体循环的转移。

In this study, we examined the effectiveness of chitosan capsules for the colon-specific delivery of prednisolone in rats. We also evaluated the effectiveness and side effect of prednisolone using chitosan capsules compared with the conventional dosage form (gelatin capsules). We found a significant increase in the concentration of prednisolone in the large intestinal mucosa when prednisolone was administered orally using chitosan capsules, as compared with the case using gelatin capsules. On the other hand, the plasma concentrations of prednisolone after oral administration using chitosan capsules were much lower than those in the case of gelatin capsules. We also assessed the effectiveness of prednisolone for the healing of trinitrobenzene sulfonic acid (TNBS)-induced colitis by measuring the rnyeloperoxidase (MPO) activities and colon wet weight/body weight (C/B) ratios. The MPO activities and C/B ratios significantly reduced when prednisolone was administered orally using chitosan capsules, in comparison with the case of gelatin capsules. Moreover, the weight of thymus, which is an index of side effect of prednisolone, remarkably decreased after oral administration of prednisolone using gelatin capsules, whereas its weight was not so much changed when prednisolone was administered orally using chitosan capsules.These findings indicated that chitosan capsules might be useful for the colon specific delivery of prednisolone and its enhanced effectiveness for the healing of colitis in rats. Moreover, chitosan capsules might be also effective for reducing the side-effect of prednisolone due to its decreased intestinal transfer to the systemic circulation.