Kofuji K, Ito T, Murata Y, Kawashima S
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa, Japan.
Biol Pharm Bull. 2001 Feb;24(2):205-8. doi: 10.1248/bpb.24.205.
Chitosan (CS) gel beads were prepared in 10% amino acid solution (pH 9) and implanted into air pouches (AP) prepared subcutaneously on the dorsal surface of mice. No inflammatory response was observed, and degradation of the beads in the AP increased as their degree of deacetylation decreased. Degradation could be altered by changing the nature of the CS or by increasing the CS concentration. The release of prednisolone (PS) in vivo from CS gel beads was similar to the release in vitro. When a suspension of PS was injected into the AP, the PS had almost completely disappeared 24 h after injection. Retention of PS in the AP was not increased by using a viscous CS solution. Alginate (Alg) gel beads, which were not degraded, released PS slowly into the AP over 3d. The in vitro release profile of PS using 1% CS (deacetylation: 70% (7B) and 80% (8B)) and 1.5% CS (deacetylation: 90% (9B)) gel beads was similar to that with Alg gel beads. However, the in vivo release of PS was affected by the degradability of the gel beads. CS7B and 8B (1%) gel beads had released PS into the AP earlier than 3 d according to their rate of degradation. CS9B (1.5%) gel beads were not degraded after 3 d and went on to release PS into the AP for 3 d similar to the release profile of Alg gel beads. CS9B (2%) gel beads were also not degraded after 3 d and the release of PS from these beads into the AP was sustained; 76% and 27% of administered PS remained in the gel beads after 1 and 3 d, respectively. Therefore, degradation and drug release of CS gel beads can be controlled by changing the structure of the gel matrix, which appears to make these beads a promising biodegradable vehicle for sustained drug delivery.
壳聚糖（CS）凝胶珠在10%氨基酸溶液（pH 9）中制备，并植入小鼠背部皮下制备的气袋（AP）中。未观察到炎症反应，随着脱乙酰度降低，气袋中凝胶珠的降解增加。通过改变CS的性质或增加CS浓度可改变降解情况。泼尼松龙（PS）从CS凝胶珠的体内释放与体外释放相似。当将PS悬浮液注入气袋时，注射后24小时PS几乎完全消失。使用粘性CS溶液并未增加PS在气袋中的保留率。未降解的藻酸盐（Alg）凝胶珠在3天内将PS缓慢释放到气袋中。使用1% CS（脱乙酰度：70%（7B）和80%（8B））和1.5% CS（脱乙酰度：90%（9B））凝胶珠的PS体外释放曲线与Alg凝胶珠相似。然而，PS的体内释放受凝胶珠降解性的影响。CS7B和8B（1%）凝胶珠根据其降解速率在3天之前就已将PS释放到气袋中。CS9B（1.5%）凝胶珠在3天后未降解，并继续将PS释放到气袋中3天，类似于Alg凝胶珠的释放曲线。CS9B（2%）凝胶珠在3天后也未降解，并且PS从这些珠子向气袋中的释放持续；给药后1天和3天，分别有76%和27%的PS保留在凝胶珠中。因此，通过改变凝胶基质的结构可以控制CS凝胶珠的降解和药物释放，这似乎使这些珠子成为一种有前途的用于持续药物递送的可生物降解载体。
