A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system.
A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system.
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DOI：
10.1016/j.biomaterials.2006.12.024
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发表时间：
2007-05
期刊：
影响因子：
14
通讯作者：
Jie Wu;Wei Wei-Wei;Lianyan Wang;Z. Su;G. Ma
中科院分区：
文献类型：
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作者：
Jie Wu;Wei Wei-Wei;Lianyan Wang;Z. Su;G. Ma
以N-[（2-羟基-3-三甲基铵）丙基]壳聚糖氯（HTCC）和聚乙二醇（PEG）与少量α-β-甘油磷酸酯（α-β- gp）简单混合，设计并制备了一种新型热敏水凝胶。研究了最佳制备条件，得到的配方在几分钟内从室温下的溶液到37℃左右的不流动的水凝胶发生了热转变。作为一种新制剂，研究了其作为鼻腔给药系统的应用潜力。它可以很容易地滴入或喷入鼻腔，并以溶液状态在鼻黏膜上扩散。该溶液经鼻腔给药后，在体温下转化为粘稠的水凝胶，使鼻黏毛清除率降低，药物释放缓慢。此外，季铵化壳聚糖作为吸收增强剂已被多篇报道广泛研究，并证明其无毒性、黏附性和打开上皮细胞间紧密连接的能力。因此，本研究将胰岛素作为模型药物包裹在该制剂中，并考察其体外释放行为。共聚焦激光扫描显微镜（CLSM）证实了该制剂能增强异硫氰酸荧光素（FITC）标记胰岛素在大鼠鼻腔中的吸收。研究了该水凝胶经鼻给药后的细胞毒性和血糖浓度的变化。水凝胶制剂在给药后至少4-5h内血糖浓度明显降低（初始血糖浓度的40-50%），且未发现明显的细胞毒性。上述结果表明，HTCC-PEG-GP制剂可作为鼻腔给药系统，改善亲水性大分子药物的吸收。
A new thermosensitive hydrogel was designed and prepared by simply mixing N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and poly(ethylene glycol) (PEG) with a small amount of α-β-glycerophosphate (α-β-GP). The optimum preparative condition was investigated, and the obtained formulation underwent thermal transition from solution below or at room temperature to non-flowing hydrogel around 37°C in several minutes. As a new formulation, its potential use as nasal drug delivery system was studied. It can be dropped or sprayed easily into nasal cavity and spread on the nasal mucosa in solution state. After being administered into nasal cavity, the solution transformed into viscous hydrogel at body temperature, which decreased nasal mucociliary clearance rate and released drug slowly. Morever, quaternized chitosan as absorption enhancer has been studied extensively in several reports and proved its non-toxicity, mucoadhesivity and the capacity to open the tight junctions between epithelial cells. Therefore, in this study insulin as a model drug was entrapped in this formulation and its release behavior in vitro was also investigated. The enhancement of absorption of fluorescein isothiocyanate (FITC)-labeled insulin in rat nasal cavity by this formulation was proved by confocal laser scanning microscopy (CLSM). The cytoxicity and the change of the blood glucose concentration after nasal administration of this hydrogel were also investigated. The hydrogel formulation decreased the blood glucose concentration apparently (40–50% of initial blood glucose concentration) for at least 4–5h after administration, and no apparent cytoxicity was found after application. These results showed that HTCC–PEG–GP formulation can be used as nasal drug delivery system to improve the absorption of hydrophilic macromolecular drugs.