Bikiaris Dimitrios, Karavelidis Vassilios, Karavas Evangelos
Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Molecules. 2009 Jul 7;14(7):2410-30. doi: 10.3390/molecules14072410.
Raloxifene HCl is a drug with poor bioavailability and poor water solubility. Furthermore nomicron pharmaceutically acceptable organic solvent has been reported before to dilute the drug. It was observed that Raloxifene HCl can be diluted in a solvent mixture of acetone/water or ethanol/water. The aim of this study was to use biodegradable polymers in order to prepare Raloxifene HCl nanoparticles. For this purpose a series of novel biodegradable poly(ethylene succinate-co-propylene adipate) P(ESu-co-PAd) polyesters were synthesized following the polycondensation method and further, poly(ethylene succinate) (PESu) and poly(propylene adipate) (PPAd) were used. The prepared polyesters were characterized by intrinsic viscosity measurements, end group analysis, enzymatic hydrolysis, Nuclear Magnetic Resonance Spectroscopy ((1H)-NMR and (13)C-NMR) and Wide-angle X-ray Diffractometry (WAXD). The drug nanoparticles have been prepared by a variation of the co-precipitation method and were studied by Wide-angle X-ray Diffractometry (WAXD), FTIR spectrometry, light scattering size distribution, Scanning Electron Microscopy (SEM) and release behavior measurements. The interactions between the polymers and the drug seem to be limited, so the drug occurs in crystalline form in all nanoparticles. The size of the nanoparticles seems to be in the range of 150-350 nm, depending on the polymer that was used. The drug release depends on the melting point and degree of crystallinity of the polyesters used. An initial high release rate was recorded followed by very slow rates of controlled release.
盐酸雷洛昔芬是一种生物利用度差且水溶性差的药物。此外，之前已有报道称使用纳米级药学上可接受的有机溶剂来稀释该药物。据观察，盐酸雷洛昔芬可在丙酮/水或乙醇/水的溶剂混合物中稀释。本研究的目的是使用可生物降解的聚合物来制备盐酸雷洛昔芬纳米颗粒。为此，采用缩聚法合成了一系列新型可生物降解的聚（琥珀酸乙烯酯 - 共 - 己二酸丙酯）P（ESu - 共 - PAd）聚酯，此外，还使用了聚（琥珀酸乙烯酯）（PESu）和聚（己二酸丙酯）（PPAd）。通过特性粘度测量、端基分析、酶水解、核磁共振光谱（（1H）-NMR和（13C）-NMR）以及广角X射线衍射（WAXD）对所制备的聚酯进行了表征。通过共沉淀法的改进制备了药物纳米颗粒，并通过广角X射线衍射（WAXD）、傅里叶变换红外光谱（FTIR）、光散射尺寸分布、扫描电子显微镜（SEM）和释放行为测量对其进行了研究。聚合物与药物之间的相互作用似乎有限，因此药物在所有纳米颗粒中均以结晶形式存在。纳米颗粒的尺寸似乎在150 - 350 nm范围内，这取决于所使用的聚合物。药物释放取决于所用聚酯的熔点和结晶度。记录到初始高释放速率，随后是非常缓慢的控释速率。
