Preparation and evaluation of radiolabeled gliclazide parenteral nanoemulsion as a new tracer for pancreatic β-cells mass

Abstract

Purpose

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.

Methods

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 in silico and in vivo in normal and diabetic rats.

Results and conclusions

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. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo 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.

Keywords:

• Iodine-125 radiolabeling
• targeting β-cells
• gliclazide
• pancreas
• diabetes mellitus
• tracer
• preclinical evaluation

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper in any way.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

O. A. El-Kawy

O. A. El-Kawy is a Senior Scientist at the Egyptian Atomic Energy Authority. He is an interdisciplinary researcher and postgraduate lecturer with a background in Pharmaceutical Sciences and Microbiology. O. A. El-Kawy is interested in synthesizing, radiolabeling, and evaluating organic compounds, nanoparticles, and pharmaceuticals for nuclear medicine applications. Over the past 18 years, his research focused on biosafety issues, radiopharmaceuticals, cancer detection and therapy, discrimination between septic and aseptic inflammations, and receptor targeting. He has represented Egypt and the scientific profession at numerous international forums and meetings.

I. T. Ibrahim

I. T. Ibrahim is a Radio Pharmacology Professor at the Egyptian Atomic Energy Authority. He is interested in radiolabeling pharmaceutical organic compounds that may have applications in radio imaging and radiotherapy. He has many publications in the field of radiolabeling in international journals. Some of his publications involve imaging of the brain, stomach, lungs, liver, and bone. Others are concerned with tumor imaging and therapy. Nanotechnology was used in much of his research to deliver or target a particular site or organ. He also has experience in teaching in the faculty of pharmacy.

H. A. Shewatah

H. A. Shewatah is currently an Organic Chemistry lecturer at the Egyptian Atomic Energy Authority. She had over ten years of teaching experience as an assistant professor at the College of Pharmacy, Umm Al-Qura University. She coauthored many research works on labeling organic compounds with Tc-99m and I-131 for radio imaging and diagnosis in the medical field.

K. M. Attalah

K. M. Attalah is an Assistant Professor of radiopharmacy at the Labeled Compounds Department, Egyptian Atomic Energy Authority. He is interested in preparing therapeutic and diagnostic radiopharmaceuticals using radioisotopes (technetium-99m and iodine-131). He is able to conduct in vitro and in vivo studies of novel dosage forms using different radiolabeling techniques and perform biodistribution studies of nanoparticles in animal models. He has some publications in international journals. He also has good experience teaching undergraduate students at the College of Pharmacy.