Attama A A, Reichl S, Müller-Goymann C C
Institut für Pharmazeutische Technologie, Technische Universität Carolo-Wilhelmina zu Braunschweig, Braunschweig, Germany.
Curr Eye Res. 2009 Aug;34(8):698-705. doi: 10.1080/02713680903017500.
The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct.
Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography.
Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water.
Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.
本研究旨在制备并评估马来酸噻吗洛尔的表面修饰固体脂质纳米粒缓释给药系统，马来酸噻吗洛尔是一种典型的眼用药物，采用人角膜构建体进行研究。
采用熔融乳化结合高压均质法制备含和不含磷脂的马来酸噻吗洛尔表面修饰固体脂质纳米粒，并通过粒径、广角X射线衍射、包封率和体外药物释放进行表征。使用改良的Franz扩散池进行药物透过人供体角膜细胞构建的角膜的转运研究，并通过高效液相色谱分析药物浓度。
结果表明，表面修饰的固体脂质纳米粒具有非常小的粒径（SM-SLN 1、SM-SLN 2、SM-SLN 3和SM-SLN 4的粒径分别为42.9±0.3nm、47.2±0.3nm、42.7±0.7nm和37.7±0.3nm），多分散指数低，包封率提高（>44%），与粒径大于160nm的未修饰脂质纳米粒相比，体外释放具有缓释特性。与马来酸噻吗洛尔在蒸馏水中的溶液相比，马来酸噻吗洛尔从表面修饰的脂质纳米粒透过角膜构建体的渗透具有缓释特性。
表面修饰的固体脂质纳米粒可为提高马来酸噻吗洛尔的眼内生物利用度提供一种有效方法。
