Chitosan for enhanced intestinal permeability:: Prospects for derivatives soluble in neutral and basic environments
Chitosan for enhanced intestinal permeability:: Prospects for derivatives soluble in neutral and basic environments
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DOI：
10.1016/s0928-0987(98)00016-5
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发表时间：
1999-01-01
影响因子：
4.6
通讯作者：
Junginger, HE
中科院分区：
文献类型：
--
作者：
Kotzé, AF;Luessen, HL;Junginger, HE
在弱酸性(pH 6.2)和中性(pH 7.3)环境中，用放射性标记物[C-14]甘露醇研究了两种壳聚糖盐，即壳聚糖盐酸盐和壳聚糖谷氨酸(0.5%和1.5%w/v)对癌细胞单层跨上皮电阻(TEER)和通透性的影响。这两种盐都可溶于浓度为1.5%w/v的酸性条件下，在pH为6.2时，孵育20分钟后，Caco-2细胞单层的TEER显著降低，降幅分别为70+/-1%(壳聚糖谷氨酸)和77+/-3%(壳聚糖盐酸盐)。与TEER结果一致，放射性标记物[C-14]-甘露醇的转运在该pH下分别增加了25倍(壳聚糖谷氨酸)和36倍(壳聚糖盐酸盐)。然而，在pH为7.4时，这两种盐都是不溶的，并被证明是无效的，因为没有发现TEER值降低或[C-14]-甘露醇转运增加。结果表明，这些壳聚糖盐在酸性环境中是一种有效的吸收促进剂。我们的结论是，需要增加溶解度的壳聚糖衍生物，特别是在中性和碱性pH值下，用作吸收促进剂，目的是在大肠和结肠的基本环境中输送治疗性化合物。(C)1998 Elsevier Science B.V.保留所有权利。
In this study the effects of two chitosan salts, namely chitosan hydrochloride and chitosan glutamate (0.5 and 1.5% w/v), on the transepithelial electrical resistance (TEER) and permeability of Caco- cell monolayers, using the radioactive marker [C-14]-mannitol, were investigated in a slightly acidic (pH 6.2) and neutral (pH 7.3) environment. Both salts are soluble in acidic conditions up to a concentration of 1.5% w/v and solutions of this strength, at a pH of 6.2, caused a pronounced lowering in the TEER of Caco-2 cell monolayers in the order of 70+/-1% (chitosan glutamate) and 77+/-3% (chitosan hydrochloride), 20 min after incubation started. In agreement with the TEER results the transport of the radioactive marker, [C-14]-mannitol, was increased 25-fold (chitosan glutamate) and 36-fold (chitosan hydrochloride), respectively, at this pH. However, at a pH of 7.4 both salts are insoluble and prove to be ineffective since no reduction in the TEER values or increase in the transport of [C-14]-mannitol were found. The results show that these chitosan salts are potent absorption enhancers in acidic environments. We conclude that there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values, for use as absorption enhancers aimed at the delivery of therapeutic compounds in the mon basic environment of the large intestine and colon. (C) 1998 Elsevier Science B.V. All rights reserved.