Hamzian Nima, Hashemi Maryam, Ghorbani Mahdi, Bahreyni Toosi Mohammad Hossein, Ramezani Mohammad
Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Pharm Res. 2017 Winter;16(1):8-21.
The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant (-value = 0.006 for SPION-PLGA-Gem and -value = 0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future work includes and investigation of radiosensitization and other application of these nanoparticles.
本研究的目的是开发一种新型多功能纳米颗粒，其在聚乳酸-羟基乙酸共聚物（PLGA）±聚乙二醇（PEG）中封装超顺磁性氧化铁纳米颗粒（SPION）和吉西他滨，以形成多功能药物递送系统。为此，通过水包油包水（W/O/W）双乳化法，在PLGA±PEG共聚物中同时合成超顺磁性氧化铁纳米颗粒（SPIONs）并将其与吉西他滨（Gem）封装在一起。考虑了用于放射增敏、热疗和诊断应用的最佳尺寸和包封率，并系统地研究了制备参数，同时研究了优化纳米颗粒的物理化学特性。然后，采用相同的优化参数制备了SPION-PLGA和PLGA-Gem纳米颗粒，并在人乳腺癌细胞系（MCF-7）中将这些纳米颗粒的毒性与吉西他滨进行了比较。当吉西他滨/聚合物等于0.04、SPION/聚合物等于0.8且每20mg聚合物中含有1%蔗糖时，获得了最佳制备参数。所有纳米颗粒的流体动力学直径均在200nm以下。吉西他滨的包封率调整为13.2%至16.1%，SPION的包封率调整为48.2%至50.1%。吉西他滨的释放动力学具有可控性。在纳米颗粒浓度等于吉西他滨的半数抑制浓度（IC50）时，PLGA-Gem和SPION-PLGA-Gem的增强率分别为1.53和1.89。统计学差异显著（与吉西他滨相比，SPION-PLGA-Gem的P值 = 0.006，PLGA-Gem的P值 = 0.015）。总之，我们成功开发了一种负载吉西他滨的超顺磁性PLGA-氧化铁多功能药物递送系统。未来的工作包括对这些纳米颗粒的放射增敏作用及其他应用进行研究。
