A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone
A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone
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DOI：
10.1007/s10856-018-6048-2
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发表时间：
2018-04-01
影响因子：
3.7
通讯作者：
Chetoni, Patrizia
中科院分区：
文献类型：
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作者：
Piras, Anna Maria;Zambito, Ylenia;Chetoni, Patrizia
亲脂性药物如地塞米松的眼部生物利用度取决于药物的水溶性和粘膜粘附/渗透。环糊精和壳聚糖经常分别用于改善药物溶解度或延长药物与粘膜的接触。虽然环糊精和壳聚糖的共价结合产生粘膜粘附药物复合物，但它们的水溶性限于酸性pH。本文报道了以甲基-β-环糊精（MCD）为接枝剂，以季铵化壳聚糖（QA-Ch 60）为载体，直接接枝甲基-β-环糊精（MCD）。所得产物是水溶性壳聚糖衍生物，在季铵化壳聚糖和环糊精之间具有10个原子长的间隔基。该衍生物能够络合模型药物地塞米松，并且对于冻干产品也观察到稳定的络合物。此外，缀合物保留了季铵化壳聚糖的典型粘膜粘附特性，并且通过体外细胞毒性评价初步评估了其作为用于眼科应用的增溶赋形剂的安全性。总的来说，观察到的特征似乎有希望用于将开发的产品未来加工成3D固体形式，例如受控药物递送系统，薄膜或药物洗脱医疗器械。
The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-beta-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.