McClean S, Prosser E, Meehan E, O'Malley D, Clarke N, Ramtoola Z, Brayden D
Elan Pharmaceutical Technologies, Biotechnology Building, Trinity College, Dublin 2, Ireland.
Eur J Pharm Sci. 1998 Apr;6(2):153-63. doi: 10.1016/s0928-0987(97)10007-0.
The use of biodegradable particles as oral delivery vehicles for macromolecular drugs was investigated. We evaluated the binding, uptake and absorption of poly-dl-lactide (PLA) micro- and nanoparticles in Caco-2 monolayers and in ileal tissue and gut associated lymphoid tissue (GALT) of anaesthetised rats and rabbits. Using a range of experimental techniques, we found that approximately 10% of administered micro- and nanoparticles were adsorbed to the apical membranes of each of the five intestinal models. Nanoparticles were found to be absorbed better than microparticles. Overall, little discrimination in uptake patterns was evident between Peyer's patch (PP) and non-PP tissue while rat ileum showed a greater uptake capacity than rabbit. Our results show that uptake of PLA particles was low capacity, size-dependent and predominantly transcellular in all systems. A low proportion of the apically-bound particles was absorbed, with uptake exclusion evident for particles >4microm. The affinity of PLA particles for intestinal epithelia and GALT needs to be greatly enhanced in order to achieve improved oral bioavailability of macromolecules.
研究了将可生物降解颗粒用作大分子药物的口服给药载体。我们评估了聚-dl-丙交酯（PLA）微米和纳米颗粒在Caco-2单层细胞以及麻醉大鼠和兔子的回肠组织和肠道相关淋巴组织（GALT）中的结合、摄取和吸收情况。通过一系列实验技术，我们发现，在所使用的五种肠道模型中，约10%的给药微米和纳米颗粒吸附于顶端膜。纳米颗粒的吸收情况优于微米颗粒。总体而言，派尔集合淋巴结（PP）组织和非PP组织在摄取模式上几乎没有明显差异，而大鼠回肠的摄取能力比兔子更强。我们的结果表明，在所有系统中，PLA颗粒的摄取能力较低、具有尺寸依赖性且主要通过跨细胞途径进行。顶端结合颗粒的吸收比例较低，对于直径>4微米的颗粒明显存在摄取排斥现象。为了提高大分子药物的口服生物利用度，需要大幅增强PLA颗粒对肠道上皮和GALT的亲和力。
