Mohamed Farahidah, van der Walle Christopher F
Pharmaceutical Sciences, University of Strathclyde, 27 Taylor St., Glasgow, UK.
Int J Pharm. 2006 Mar 27;311(1-2):97-107. doi: 10.1016/j.ijpharm.2005.12.016. Epub 2006 Jan 18.
We describe the fabrication of DNA-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules with novel surface morphologies that will be of use in pulmonary delivery. Our approach was to examine surface morphology and DNA encapsulation efficiency as a function of primary emulsion stability; using two surfactant series based on hydrophile-lipophile balance and hydrophobe molecular weight. Hydrophilic non-ionic surfactants yielded the most stable water-in-dichloromethane emulsions (HLB values >8). These surfactants normally favor convex (o/w) interfacial curvatures and therefore this atypical behavior suggested a relatively high surfactant solvation in the dichloromethane 'oil' phase. This was consistent with the large fall in the glass transition temperature for microspheres prepared with Tween 20, which therefore efficiently penetrated the PLGA matrix and acted as a plasiticizer. Blends of Pluronic triblock copolymers performed poorly as water-in-dichloromethane emulsifiers, and were therefore used to generate hollow microspheres ('microcapsules') with low densities (0.24 g/cm(3)). Although the Pluronic-stabilized emulsions resulted in lower DNA loading (15-28%), microspheres (approximately 8 microm) with novel dimpled surfaces were fabricated. The depth and definition of the dimples was greatest for triblock copolymers with high MW hydrophobe blocks. By cascade impaction, the geometric mean weight diameter of the microcapsules was 3.43 microm, suggesting that they will be of interest as biodegradable pulmonary delivery vehicles.
我们描述了具有新型表面形态的载DNA聚乳酸-乙醇酸共聚物（PLGA）微胶囊的制备方法，该微胶囊将用于肺部给药。我们的方法是研究表面形态和DNA包封效率与初级乳液稳定性的关系；使用基于亲水亲油平衡和疏水基团分子量的两个表面活性剂系列。亲水性非离子表面活性剂产生了最稳定的二氯甲烷包水乳液（HLB值>8）。这些表面活性剂通常有利于凸面（水包油）界面曲率，因此这种非典型行为表明表面活性剂在二氯甲烷“油”相中具有较高的溶剂化作用。这与用吐温20制备的微球的玻璃化转变温度大幅下降一致，因此吐温20能有效穿透PLGA基质并起到增塑剂的作用。普朗尼克三嵌段共聚物作为二氯甲烷包水乳化剂的性能较差，因此被用于制备低密度（0.24 g/cm³）的中空微球（“微胶囊”）。虽然普朗尼克稳定的乳液导致较低的DNA载量（15 - 28%），但制备出了具有新型凹坑表面的微球（约8微米）。对于具有高分子量疏水基团嵌段的三嵌段共聚物，凹坑的深度和清晰度最大。通过级联撞击，微胶囊的几何平均重量直径为3.43微米，这表明它们作为可生物降解的肺部给药载体将具有吸引力。
