Siafaka Panoraia I, Barmbalexis Panagiotis, Bikiaris Dimitrios N
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124, Macedonia, Greece.
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124, Macedonia, Greece.
Eur J Pharm Sci. 2016 Jun 10;88:12-25. doi: 10.1016/j.ejps.2016.03.021. Epub 2016 Mar 30.
In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR.
在本研究中，对一系列由聚乳酸/聚己二酸丁二醇酯（PLA/PBAd）电纺共混物组成的新型制剂进行了研究，将其作为来氟米特的活性代谢物——特立氟胺（TFL）的控释基质。使用不同比例的PLA和PBAd制备混合物，以生产具有不同特性的纳米纤维基质。通过差示扫描量热法（DSC）和X射线衍射法（XRD）对共混聚合物纤维进行混溶性研究。使用磷酸盐缓冲盐溶液在37°C下评估制备纤维的水解降解情况。将不同浓度的（TFL）（5、10、15wt.%）掺入纳米纤维中，以研究在37°C下模拟体液（SBF）中的药物释放行为。通过傅里叶变换红外光谱（FTIR）、DSC和XRD对载药纳米纤维制剂进行进一步表征。凝胶渗透色谱（GPC）分析用于评估TFL的释放机制。使用人工神经网络（ANN）和多元线性回归（MLR）模型来评估PBAd（X1）和TFL（X2）的含量百分比对初始突释效应和溶解行为的影响。发现PLA/PBAd纳米纤维的直径因所用聚酯的比例和添加药物的不同而不同。TFL以无定形形式掺入聚合物纳米纤维内部。体外释放研究表明，药物释放行为与纳米纤维的尺寸、药物负载量以及特定时间后的基质降解相关。与MLR相比, ANN溶解模型显示出更高的相关效能。
