摘要
目的制备一种具有生物黏附性的双氯芬酸温度敏感水凝胶用于眼部局部给药,以提高其生物利用度。方法选用泊洛沙姆F-127(pluronic F-127)为药物载体,结合使用生物黏附性天然高分子多糖——羧甲基壳聚糖,制备一种具有生物黏附性的双氯芬酸水凝胶,考察体系中羧甲基壳聚糖浓度以及双氯芬酸浓度对于凝胶的相转变温度的影响,并采用流变仪考察其流变学性能。同时以家兔为模型,对其眼部局部给药之后的体内药动学进行考察。结果水凝胶体系中的羧甲基壳聚糖浓度以及双氯芬酸浓度对于泊洛沙姆F-127水凝胶的相转变温度没有明显的影响。流变学性能检测显示6.3×10^(-3)mol·L^(-1)双氯芬酸水凝胶在24℃出现相转变。体外释放实验结果显示与双氯芬酸水溶液相比,双氯芬酸水凝胶具有明显的缓慢释放行为。家兔眼表给药之后(每眼50μL),双氯芬酸水溶液制剂给药的兔子前房中药物浓度在给药后45 min达到最大值2.45 g·L^(-1),而采用双氯芬酸水凝胶制剂给药的兔子前房药物浓度在给药后45 min也达到最大值5.75 g·L^(-1)。结论所制备的生物黏附性双氯芬酸温度敏感水凝胶能有效地提高眼部局部给药的生物利用度,延长药物半衰期,减少给药次数。
AIM To prepare a bioadhensive diclofenac thermosensitive hydrogel to improve its bioavail- ability for ocular application. METHODS Poloxamer F-127 （pluronic F-127）, a thermosensitive polymer used as a vector was combined with a polyssaccride （carboxymethyl chitosan） to prepare a bioadhensive diclofenac thermosensitive hydrogel. The properties of hydrogel was examined by rheometer and the effects of concentration alterations of chitosan and diclofenac on hydrogel gelation were also investigated. In the rabbit model, the pharmacokinetics of diclofenac and diclofenac hydrogel were monitored. RESULTS Neither carboxymethyl chitosan or diclofenac altered the gelation behavior of hydrogel. Rheological analysis showed that the diclofenac hydrogel underwent sol-gel transition at 24 ℃. Diclofenac released from hydrogel was slower compared with that of diclofenac solution. In vivo study showed that the group treated with diclofenac hydrogel （50 μL per eye） reached the max concentration of 5.75 g.L^-1 after 45 min, while the group treated with diclofenac eye drop reached the max concentration of 2.45 g.L^-1 after 45 rain. CONCLUSION The administration of our preparedbioadhensive diclofenac hydrogel greatly improves the drug bioavailability, prolongs drug half-time, and reduces the frequency of administration.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2013年第10期819-823,共5页
Chinese Journal of New Drugs and Clinical Remedies
关键词
泊洛沙姆
水凝胶
双氯芬酸
生物利用度
poloxamer
hydrogel
diclofenac sodium
in vitro
biological availability
