Shome Debraj, Poddar Neha, Sharma Vinay, Sheorey Uday, Maru Girish B, Ingle Arvind, Sarin Rajiv, Banavali Shripad, Dikshit Rajesh, Jain Vandana, Honavar Santosh, Bellare Jayesh
Department of Ocular Oncology, Tata Memorial Center, Mumbai, India.
Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5896-900. doi: 10.1167/iovs.09-3914. Epub 2009 Jul 23.
To compare intravitreal concentration (VC) of commercially available carboplatin (CAC) and the novel nanomolecule carboplatin (NMC), after periocular injection.
The study was a comparative animal study involving 24 white Sprague-Dawley rats, aged between 6 weeks and 3 months. CAC was bound with a nanoparticulate carrier by co-acervation with a biocompatible and biodegradable protein BSA (bovine serum albumin). The particulate size, binding, and structure of the carrier was analyzed with dynamic light-scattering electron microscopy, FTIR (Fourier transform infrared) spectroscopy, and SDS-polyacrylamide gel electrophoresis. Twenty-four white rats were anesthetized. The right eye of each rat was injected with periocular CAC (1 mL) and the left eye with NMC (1 mL) by a trained ophthalmologist. Four mice each were euthanatized at days 1, 2, 3, 5, 7, 14, and 21 and both eyes were enucleated. The intravitreal concentrations of commercial carboplatin and nanomolecule carboplatin were determined with HPLC (high-performance liquid chromatography). Data were analyzed with the paired t-test. The main outcome measure was intravitreal concentrations CAC and NMC over time.
The NMC vitreal concentration was higher than the CAC concentrations in all animals, until day 7 (P = 0.0001). On days 14 and 21, the CAC vitreal concentration was higher than the NMC concentrations in all animals (P = 0.0002). Overall, the mean vitreal concentration of NMC was greater than CAC.
Nanoparticulate-bound carboplatin has greater transscleral transport than commercially available carboplatin, especially in the first week after injection and may help enhance the proven adjuvant efficacy of periocular carboplatin over and above systemic chemotherapy in treating human retinoblastoma, especially those with vitreal seeds. This trial is being published to establish a proof of principle for this method of therapy.
比较市售卡铂（CAC）和新型纳米分子卡铂（NMC）经眼周注射后的玻璃体内浓度（VC）。
本研究为比较性动物研究，涉及24只6周龄至3月龄的白色Sprague-Dawley大鼠。通过与生物相容性和可生物降解的蛋白质牛血清白蛋白（BSA）凝聚，将CAC与纳米颗粒载体结合。用动态光散射电子显微镜、傅里叶变换红外（FTIR）光谱和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析载体的颗粒大小、结合情况和结构。24只白色大鼠麻醉后，由训练有素的眼科医生对每只大鼠的右眼注射眼周用CAC（1 mL），左眼注射NMC（1 mL）。在第1、2、3、5、7、14和21天，每组处死4只小鼠并摘除双眼。用高效液相色谱（HPLC）测定市售卡铂和纳米分子卡铂的玻璃体内浓度。数据采用配对t检验进行分析。主要观察指标为随时间变化的玻璃体内CAC和NMC浓度。
在第7天之前，所有动物的NMC玻璃体内浓度均高于CAC浓度（P = 0.０００１）。在第14天和21天，所有动物的CAC玻璃体内浓度高于NMC浓度（P = 0.０００２）。总体而言，NMC的平均玻璃体内浓度高于CAC。
纳米颗粒结合的卡铂比市售卡铂具有更强的经巩膜转运能力，尤其是在注射后的第一周，这可能有助于增强眼周卡铂在治疗人类视网膜母细胞瘤方面优于全身化疗的已证实的辅助疗效, 特别是对于有玻璃体种植的患者。本试验旨在为这种治疗方法建立原理验证。
