Characterization, optimization, and in vitro evaluation of Technetium-99m-labeled niosomes

Abstract

Background and purpose: Niosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m (99mTc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize 99m Tc-labeled niosomes. Methods: Niosomes were prepared from a mixture of sorbitan monostearate 60, cholesterol, and synthesized D-α-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid (synthesis confirmed by 1 H and 13 C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99m Tc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl 2 ⋅H 2 O), pH, and incubation time were evaluated. In vitro stability of radiolabeled niosomes was studied in 0.9% saline and human serum at 37°C for up to 8 hours. Results: Niosomes had an average particle size of 110.2±0.7 nm, polydispersity index of 0.229±0.008, and zeta potential of −64.8±1.2 mV. Experimental data revealed that 30 µg/mL of SnCl 2 ⋅H 2 O was the optimal concentration of reducing agent required for the radiolabeling process. The pH and incubation time required to obtain high radiolabeling efficiency was pH 5 and 15 minutes, respectively. 99m Tc-labeled niosomes exhibited high radiolabeling efficiency (>90%) and showed good in vitro stability for up to 8 hours. Conclusion: To our knowledge, this is the first study published on the surface chelation of niosomes with 99m Tc. The formulated 99m Tc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future.