Capillary Video-Microscopy on the Release of Water-Soluble Drugs from Double-Emulsion Globules into Giant Liposomes

abstractcts - 0075712 k。这是一项探索性资助，其假设是毛细管视频显微镜可以独特地揭示水溶性药物从双乳微球释放机制的关键方面，并将其转运到邻近的模仿生物细胞的巨型脂质体中。目的是阐明控制这些机制的现象，并对其进行控制，最终决定可溶乳剂作为药物输送系统的成功应用。以盐酸麻黄碱（EPH HCI）为模型水溶性药物，包封于W1/0/W2微球的W1小室中，油膜为石蜡油。研究了油溶性非离子表面活性剂Span-80（山梨醇单油酸酯）和水溶性非离子表面活性剂Tween-80对微球稳定性和药物释放的影响。NaCl可调节双乳液微球的渗透压梯度。通过使用Narishige PB-7微移液器将熔点管（1.1-1.2 mm id x 100 mm）从中间拉出微细毛细管（~ 200um id, 10 200um）（见图2）。尖端精细的注射和显微操作移液器将通过从其一端拔出微管（Microcapes. 0.688 mm i.d X 78 mm）来成形，从而产生外径为10-15 um的尖端。微移液器将在未来用microgorge （Narishige MF-9，见图3）塑成，这样我们就可以抛光移液器的末端或将其弯曲成所需的形状。要制备W1/0/W2微球，首先将纯水或盐水溶液填充在微毛细管中。然后插入一个装满油（含有油溶性表面活性剂）的微管，并将注入一个大的油滴。随后，内部的麻黄碱-盐酸溶液液滴将通过与产生油滴相同的程序形成油滴。这种制备微球的过程将导致W1相和W2相之间的渗透压梯度，从而导致水溶性药物的释放。每次实验将使用单个球，并在显微镜下观察该球中的完整输运过程。在那些将监测EPH HCI转移到血管的实验中，将首先通过电生成用1-棕榈酰- 20油酰-sn-甘油-3-磷酸胆碱制备一个巨大的囊泡。通过在W1和W2中使用不同的盐度以及在W1中使用EOPH HCI浓度，我们将知道在它们的条件下，水溶性物质是通过“膨胀-分解”机制传递的。破裂前所需的时间将作为药物释放速度的量度。影响破裂时间的一个明显的几何因素是W1液滴的大小。由于较小的W1液滴将需要更长的时间才能破裂，因此这种液滴的多分散性将导致释放时间延长，因此将作为控制释放的工具进行研究。在这些不会产生膨胀和破裂的盐度条件下，水会通过一些促进扩散的机制从W1和W2中运输，如反胶束作用、自发乳化作用、水合表面活性剂或层状促进运输。我们将确定在不同条件下，受各种表面活性剂组合和配方影响的药物释放动力学，这些组合和配方将有利于某些机制。为了可视化释放的物质从W1/0/W2球到邻近的巨囊泡的运输，将在盐酸麻黄碱溶液中加入荧光染料（n -甲基羟基碘化喹啉）。为了模拟体内可能的释放情况，将研究接触和非接触的双乳球状体和巨大囊泡的构型。为了研究小球-囊泡接触下的药物转移，轻轻推动巨囊泡，视觉上接触到W1/0/W2小球。

ABSTRACTCTS-0075712K. PapadopoulosTulane UniversityThis is an exploratory grant for which the hypotheses is that Capillary Video-microscopy can uniquely reveal key aspects of the release mechanisms of water-soluble drugs from double-emulsion globules and their transport into neighboring giant liposomes that mimic biological cells. The goal is to elucidate the phenomena which govern these mechanisms and the control of which will ultimately decide the successful application of soluble emulsions as drug-delivery systems.Ephedrine hydrochloride (EPH HCI) will be used as the model water-soluble drug, encapsulated in the W1 compartment of a W1/0/W2 globule, and the oil membrane will be paraffin oil. Oil-soluble, nonionic surfactant Span-80 (sorbitan monooleate) and water-soluble, non-ionic surfactant Tween-80 will be studied as factors of both globule stability and drug release. The osmotic pressure gradients in the double-emulsion globules will be adjusted through NaCl.Microcapillaries (~200 um i.d., 10 200 um) will be fabricated from melting point tubes (1.1-1.2 mm i.d. x 100 mm) by pulling them in the middle using a Narishige PB-7 micropipette puller (see Picture 2). Injection and micromanipulation pipettes with fine tip will be shaped by pulling microtubes (Microcapes. 0.688 mm i.d. X 78 mm) from one of their ends so as to produce a tip of outside diameter 10-15 um. Micropipettes will be future fashioned with a microgorge (Narishige MF-9, see picture 3), thus allowing us to polish the end of the pipette or to bend it to a desired shape.To prepare a W1/0/W2 globule, a microcapillary will be filled with pure water or a saline solution at first. A micropipette filled with oil (containing oil-soluble surfactants) will then be inserted and will inject a large oil drop. Subsequently, and internal ephedrine-hydrochloride-solution droplet will be formed into the oil via the same procedure as the one that produces the oil drop. This globule preparation procedure will lead to an osmotic pressure gradient between W1 and W2 phases, which will cause the release of the water-soluble drug. A single globule will be used in each experiment and the complete transport process in this globule will be observed microscopically. In those experiments that will monitor the transfer of EPH HCI to a vessel, a giant vesicle will first be prepared with 1-palmitoyl-2oleoyl-sn-glycero-3-phosphocholine through electroformation.By using different salinities in W1 and W2 and EOPH HCI concentrations in W1 we will know under their conditions the water-soluble is delivered by a "swelling-breakdown" mechanism. The time needed before rupture will be used as a measure of the drug release rate. An obvious geometrical factor that will effect the time of rupture is the size of the W1 droplets. Since smaller W1 droplets will take longer to burst, polydisperity in such droplets should lead to prolonged release, and thus will be studied as a tool to control delivery.Under those salinity conditions that will not produce swelling and breakdown, water will transport from W1 and W2 via some diffusion-facilitating mechanisms, such as reverse micellization, spontaneous emulsification, hydrated-surfactant or lamellar-facilitated transport. We will determine the kinetics of such drug release as effected by various surfactant combinations and formulations that will favor certain mechanisms over others under different conditions.To visualize the transport of the released material from the W1/0/W2 globule to the neighboring giant vesicle, aqueous fluorescent dye (N-Methylhdroxy-quinolinium iodide) will be added to ephedrine hydrochloride solution. In order to simulate possible release situations in the body, both contact and non-contact a configuration of a double-emulsion globule and a giant vesicle will be studied. To study drug transfer under globule-vesicle contact, the giant vesicle will be pushed gently so as to visually touch the W1/0/W2 globule.