Dalpiaz A, Mezzena M, Scatturin A, Scalia S
Department of Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy.
Int J Pharm. 2008 May 1;355(1-2):81-6. doi: 10.1016/j.ijpharm.2007.11.044. Epub 2007 Nov 29.
The objective of this study was to prepare solid lipid microparticles (SLMs) loaded with the polar adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA). The microparticles were produced by the conventional hot emulsion technique, using different lipidic carriers (tristearin, glyceryl behenate and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The controlled release of CPA was achieved only with stearic acid microparticles. This phenomenon has been attributed to direct acid-base interactions between the basic nitrogen atoms of CPA and stearic acid. These SLMs were characterized by release studies, scanning electron microscopy and powder X-ray diffraction analyses. The obtained particles showed proper features in terms of morphology and size distribution (3.2-10.3microm), with a drug loading of 0.15+/-0.04%. The influence of the SLMs carrier system on CPA stability was investigated in vitro using human whole blood. The degradation kinetic of microparticle-entrapped CPA was significantly lower from that measured for the free CPA. The overall results indicate that it was possible to achieve the encapsulation and controlled release of a polar drug, such as CPA, within a lipid matrix without resorting to the complex methods generally used for the preparation of these systems.
本研究的目的是制备负载极性腺苷 A1 受体激动剂 N6-环戊基腺苷（CPA）的固体脂质微粒（SLM）。这些微粒采用传统的热乳化技术制备，使用不同的脂质载体（三硬脂酸甘油酯、山嵛酸甘油酯和硬脂酸）以及氢化磷脂酰胆碱作为表面活性剂。仅硬脂酸微粒实现了 CPA 的控释。这种现象归因于 CPA 的碱性氮原子与硬脂酸之间的直接酸碱相互作用。这些 SLM 通过释放研究、扫描电子显微镜和粉末 X 射线衍射分析进行表征。所获得的微粒在形态和尺寸分布（3.2 - 10.3 微米）方面呈现出合适的特征，载药量为 0.15±0.04%。使用人全血在体外研究了 SLM 载体系统对 CPA 稳定性的影响。微粒包封的 CPA 的降解动力学明显低于游离 CPA 的降解动力学。总体结果表明，无需采用通常用于制备这些系统的复杂方法，就有可能在脂质基质中实现极性药物（如 CPA）的包封和控释。
