El-Kawy O A, Ibrahim I T, Shewatah H A, Attalah K M
Egyptian Atomic Energy Authority, Cairo, Egypt.
Int J Radiat Biol. 2023;99(11):1738-1748. doi: 10.1080/09553002.2023.2204914. Epub 2023 Apr 25.
The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing β-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the β-cells of the pancreas.
Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated and in normal and diabetic rats.
The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of -45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic β-cells.
本研究旨在开发并评估一种基于格列齐特的放射性药物，用于靶向和评估β细胞量。格列齐特是一种抗糖尿病药物，能特异性结合胰腺β细胞特有的磺脲类受体。
通过亲电取代反应，优化条件用放射性碘对格列齐特进行放射性标记。然后，采用热均质化随后超声处理的方法，将其配制成使用橄榄油和卵磷脂的纳米乳剂系统。评估该系统用于肠胃外给药和药物释放的适用性。然后，在正常和糖尿病大鼠中对该示踪剂进行评估。
获得了标记化合物，其放射化学产率高（99.3±1.1%）且稳定性良好（>48小时）。放射性标记的纳米乳剂平均液滴尺寸为24.7nm，多分散指数为0.21，ζ电位为-45.3mV，pH值为7.4，渗透压为285.3mOsm/kg，粘度为1.24mPa.s，表明适用于肠胃外给药。评估表明标记不影响格列齐特的生物活性。阻断研究进一步支持了这一观点。静脉注射纳米乳剂后，在注射后1小时和4小时，正常大鼠的胰腺摄取量最高（分别为19.57±1.16和12±0.13%ID），而糖尿病大鼠的摄取量分别为8.51±0.16和5±0.13%ID。所有结果均支持放射性碘化格列齐特纳米乳剂作为胰腺β细胞示踪剂的可行性。
