Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, No 24 Tongjia Xiang, Nanjing 210009, China.
Int J Pharm. 2011 Feb 14;404(1-2):250-6. doi: 10.1016/j.ijpharm.2010.11.013. Epub 2010 Nov 17.
This study was aimed to evaluate the potential use of a drug delivery system, drug-layered double hydroxide (LDH) nanocomposites for ocular delivery. Diclofenac was successfully intercalated into Zn-Al-NO(3)-LDH by coprecipitation method. The nanocomposites were characterized by particle size, elemental chemical analysis, thermogravimetric analysis, etc. A tilt bilayer of diclofenac molecules formed in the interlayer with the gallery height of 1.868 nm. In vivo precorneal retention studies were conducted with diclofenac sodium (DS) saline, diclofenac-LDH nanocomposite dispersion, 2% polyvinylpyrrolidone (PVP) K30-diclofenac-LDH nanohybrid dispersion and 10% PVP K30-diclofenac-LDH nanohybrid dispersion, separately. Compared with DS saline, all the dispersions have extended the detectable time of DS from 3h to 6h; C(max) and AUC(0-t) of diclofenac-LDH nanocomposite dispersion showed 3.1-fold and 4.0-fold increase, respectively; C(max) and AUC(0-t) of 2% PVP K30-LDH nanohybrid dispersion were about 5.3-fold and 6.0-fold enhancement, respectively. Results of the Draize test showed that no eye irritation was demonstrated in rabbits after single and repeated administration. These results suggest that this novel ocular drug delivery system appears to offer promise as a means to improving the bioavailability of drugs after ophthalmic applications.
本研究旨在评估药物传递系统——药物层状双氢氧化物（LDH）纳米复合材料在眼部给药中的潜在应用。采用共沉淀法将双氯芬酸钠成功插入 Zn-Al-NO（3）-LDH 中。通过粒径、元素化学分析、热重分析等对纳米复合材料进行了表征。在层间形成了倾斜的双层双氯芬酸钠分子，层间距为 1.868nm。分别用双氯芬酸钠生理盐水、双氯芬酸钠-LDH 纳米复合材料分散体、2%聚乙烯吡咯烷酮（PVP）K30-双氯芬酸钠-LDH 纳米杂化物分散体和 10%PVP K30-双氯芬酸钠-LDH 纳米杂化物分散体进行了体内角膜前滞留研究。与 DS 生理盐水相比，所有分散体均将 DS 的可检测时间从 3h 延长至 6h；双氯芬酸钠-LDH 纳米复合材料分散体的 C（max）和 AUC（0-t）分别增加了 3.1 倍和 4.0 倍；2%PVP K30-LDH 纳米杂化物分散体的 C（max）和 AUC（0-t）分别提高了约 5.3 倍和 6.0 倍。Draize 试验结果表明，单次和重复给药后兔子均未表现出眼部刺激。这些结果表明，这种新型眼部药物传递系统有望提高眼部应用后药物的生物利用度。
