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

在这项研究中，我们研究了壳聚糖胶囊对大鼠结肠特异性递送强的松龙的有效性。我们还比较了使用壳聚糖胶囊的强的松龙与常规剂型（明胶胶囊）的疗效和副作用。我们发现，与使用明胶胶囊的病例相比，口服壳聚糖胶囊的强的松龙在大肠黏膜中的浓度显著增加。另一方面，口服壳聚糖胶囊的泼尼松龙血浆浓度明显低于口服明胶胶囊的泼尼松龙血浆浓度。我们还通过测量脊髓过氧化物酶（MPO）活性和结肠湿重/体重（C/B）比来评估强的松龙对三硝基苯磺酸（TNBS）诱导结肠炎愈合的有效性。与明胶胶囊相比，壳聚糖胶囊口服强的松龙时，MPO活性和C/B比值显著降低。此外，使用明胶胶囊口服强的松龙后，胸腺重量显著下降，而使用壳聚糖胶囊口服强的松龙时，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特异性递送和其对大鼠结肠炎愈合的增强效果。此外，壳聚糖胶囊也可能有效减少强的松龙的副作用，因为它可以减少肠道向体循环的转移。

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.