Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Colloids Surf B Biointerfaces. 2013 Oct 1;110:339-46. doi: 10.1016/j.colsurfb.2013.04.045. Epub 2013 May 4.
In this study, flurbiprofen (FB) loaded poly(d,l-lactide-co-glycolide) (PLGA) and PLGA with poly(ethylene glycol) (PLGA-PEG) nanospheres (NSs) with and without hydroxypropyl-β-cyclodextrin (HPβCD) were developed as skin controlled delivery systems. X-ray diffraction was used to determine the physical state of the entrapped drug. Results showed that the drug in PLGA NSs was present in the form of a molecular dispersion (dissolved state) in the polymers, whereas in PLGA-PEG NSs, the drug was present in both molecular dispersion and crystalline forms. Furthermore, HPβCD provided solubilization of the free FB present on the surface of the PLGA-PEG NSs and a complete amorphosization of the drug was obtained. Optical analyses using TurbiscanLab(®) demonstrated that HPβCD provided an efficient steric stability of the NSs, preventing particle aggregation. The ex vivo permeation profiles of the NSs and conventional FB solution were evaluated using human skin. Results demonstrated that only PLGA-PEG NSs showed slight permeation improvement. However, after 24h, the FB retained in the skin was about 9-fold higher with NSs compared with the control solution, attributed to the reservoir effect of NSs acting as a depot, sustaining the drug and limiting its systemic absorption. In vivo performance of NSs was evaluated by assessing anti-inflammatory efficacy in TPA-induced mouse ear edema. Topically applied NSs significantly decreased in vivo inflammation compared to the control solution and the anti-inflammatory efficacy of HPβCD NSs was stronger than NSs without HPβCD. In vivo skin irritation evaluated by the in vivo Draize test showed no irritation of the formulations tested.
在这项研究中，研制了负载氟比洛芬（FB）的聚（D，L-丙交酯-共-乙交酯）（PLGA）和聚（乙二醇）（PLGA-PEG）纳米球（NS）以及含有和不含有羟丙基-β-环糊精（HPβCD）的 NS，作为皮肤控制释放系统。X 射线衍射用于确定包封药物的物理状态。结果表明，PLGA NS 中药物以分子分散（溶解状态）的形式存在于聚合物中，而在 PLGA-PEG NS 中，药物既以分子分散形式存在，又以结晶形式存在。此外，HPβCD 提供了表面游离 FB 的增溶作用，并且药物完全非晶化。使用 TurbiscanLab（®）进行的光学分析表明，HPβCD 为 NS 提供了有效的空间稳定性，防止了颗粒聚集。使用人体皮肤评估 NS 和常规 FB 溶液的体外渗透曲线。结果表明，只有 PLGA-PEG NS 显示出轻微的渗透改善。然而，24 小时后，与对照溶液相比，NS 保留在皮肤中的 FB 约增加了 9 倍，这归因于 NS 作为储库的缓释作用，持续释放药物并限制其全身吸收。通过评估 TPA 诱导的小鼠耳肿胀中的抗炎功效来评估 NS 的体内性能。与对照溶液相比，局部应用 NS 显著降低了体内炎症，并且含有 HPβCD 的 NS 的抗炎功效强于不含 HPβCD 的 NS。通过体内 Draize 试验评估的体内皮肤刺激性表明，所测试的制剂没有刺激性。
