Andrisano V, Bartolini M, Bertucci C, Cavrini V, Luppi B, Cerchiara T
Department of Pharmaceutical Sciences, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
J Pharm Biomed Anal. 2003 Aug 8;32(4-5):983-9. doi: 10.1016/s0731-7085(03)00200-0.
Amphiphilic copolymers have been the object of growing scientific interest due to their ability to form polymeric micelles in aqueous environments entrapping lipophilic drugs in their inner core. In this study, polyvinylalcohol substituted with oleic acid was employed as an amphiphilic micellar carrier for folic acid (FA), a model drug similar for its chemical-physical characteristics to methotrexate. In order to investigate the stability of the polymeric micelles, the drug incorporation and the kinetic aspects of drug release from these systems, selective analytical methods are required. The development of three analytical methods suitable for selectively identifying and reliably determining FA contained in the micelles and in the delivery systems is reported. UV derivative (first and second order) spectrophotometry was first applied to the aqueous solution of the FA containing micelles obtained at pH 9.0 and provided a characteristic spectral profiling with sharp peaks, related to the analyte, whose amplitude was used for quantitative application. A second approach involved a solid phase extraction (strong anion exchanger), which provided an effective clean up of the FA micelles solution, allowing accurate analysis to be performed also by a conventional spectrophotometric method. A RP-HPLC method, selectively supplying the FA separation from the micelles' components, was then used as a reference method to determine the accuracy of the spectrophotometric methods. These methods were applied to various micelle composition and to the delivery system study.
两亲性共聚物因其在水性环境中形成聚合物胶束并将亲脂性药物包裹在其内核中的能力而受到越来越多的科学关注。在本研究中,用油酸取代的聚乙烯醇被用作叶酸(FA)的两亲性胶束载体,FA是一种在化学物理特性上与甲氨蝶呤相似的模型药物。为了研究聚合物胶束的稳定性、药物包封率以及这些体系中药物释放的动力学方面,需要选择性分析方法。本文报道了三种适用于选择性识别和可靠测定胶束及给药系统中FA的分析方法。紫外导数(一阶和二阶)分光光度法首先应用于在pH 9.0条件下获得的含FA胶束的水溶液,得到了与分析物相关的具有尖锐峰的特征光谱图,其峰高用于定量分析。第二种方法涉及固相萃取(强阴离子交换剂),它有效地净化了FA胶束溶液,也使得采用常规分光光度法进行准确分析成为可能。然后,一种能选择性地将FA与胶束成分分离的反相高效液相色谱法被用作参考方法,以确定分光光度法的准确性。这些方法被应用于各种胶束组成以及给药系统的研究。