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

在这项研究中，我们研究了几丁糖胶囊的有效性，结肠特异性提供泼尼松龙在大鼠。我们还评价了泼尼松龙使用壳聚糖胶囊与常规剂型（明胶胶囊）相比的有效性和副作用。我们发现，泼尼松龙在大肠粘膜中的浓度显着增加时，泼尼松龙口服使用壳聚糖胶囊，与使用明胶胶囊的情况相比。另一方面，使用壳聚糖胶囊口服给药后泼尼松龙的血浆浓度远低于明胶胶囊的情况。我们还通过测量髓过氧化物酶（MPO）活性和结肠湿重/体重（C/B）比值来评估泼尼松龙对三硝基苯磺酸（TNBS）诱导的结肠炎愈合的有效性。与明胶胶囊相比，壳聚糖胶囊口服泼尼松龙后，MPO活性和C/B比值显著降低。此外，作为泼尼松龙副作用指标的胸腺重量在口服泼尼松龙明胶胶囊后显著降低，而口服泼尼松龙壳聚糖胶囊后胸腺重量变化不大，表明壳聚糖胶囊可能有助于泼尼松龙的结肠定位给药，增强其对大鼠结肠炎的治疗效果。此外，壳聚糖胶囊也可能是有效的减少泼尼松龙的副作用，由于其减少肠道转移到体循环。

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.