Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems
Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems
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DOI：
10.1016/j.jconrel.2015.06.015
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发表时间：
2015-08-28
影响因子：
10.8
通讯作者：
Gordeev, Sergey N.
中科院分区：
文献类型：
--
作者：
Garvie-Cook, Hazel;Frederiksen, Kit;Gordeev, Sergey N.
将脂质中链甘油三酯（MCT）纳入聚合物成膜系统（FFS）用于局部给药的效果已被评估。首先，测定了具有代表性的皮肤病药物倍他米松-17-戊酸酯（BMV）在含有和不含MCT的疏水性聚丙烯酸酯共聚物或亲水性羟丙基纤维素的FFS中的体外释放量。在MCT的存在下，两种聚合物的释放都增强了。用MCT对FFS进行原子力显微镜成像和纳米压痕显示，两相结构薄膜具有较软的夹杂物（直径0.5至4 μ m），周围是较刚性的结构。拉曼光谱化学作图表明，MCT主要局限于聚合物内部的包裹体，而包裹体主要存在于周围的膜中。BMV分布在整个膜内，但更集中在包裹体外。此外，虽然BMV在疏水膜中溶解得更好，但在亲水膜中的MCT包裹体中溶解得更容易，这表明BMV更容易从聚合物的这些较软区域扩散，并解释了所观察到的释放增强。其次，离体皮肤渗透研究清楚地表明，疏水性FFS对BMV的吸收高于亲水性聚合物，至少部分原因是前者具有更强的抗成核效率。药物很快被吸收到SC中，然后在一段持续的时间内持续扩散到较低的、有活力的皮肤层。在MCT存在的情况下，BMV的总体吸收增加，为进一步优化FFS作为简单、方便和持续的局部治疗配方提供了基础。(C) 2015 Elsevier B.V.版权所有
The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4 mu m in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy. (C) 2015 Elsevier B.V. All rights reserved.