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. 2019 Feb 12:14:1101-1117.
doi: 10.2147/IJN.S184912. eCollection 2019.

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

Leanne De Silva  1 , Ju-Yen Fu  2 , Thet Thet Htar  1 , Saravanan Muniyandy  3 , Azahari Kasbollah  4 , Wan Hamirul Bahrin Wan Kamal  4 , Lay-Hong Chuah  1   5
Affiliations

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

Leanne De Silva et al. Int J Nanomedicine. .

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 99mTc-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 1H and 13C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99mTc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl2·H2O), 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 SnCl2·H2O 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. 99mTc-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 99mTc. The formulated 99mTc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future.

Keywords: drug delivery; formulation; nanocarriers; nanotechnology; nuclear imaging; radiolabeling.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Chemical structure of synthesized TPGS-DTPA. Abbreviation: TPGS-DTPA, d-α-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid.
Figure 2
Figure 2
FTIR spectra of DTPA anhydride, TPGS and synthesized TPGS-DTPA. Abbreviations: DTPA, diethylenetriaminepentaacetic acid; FTIR, Fourier-transform infrared spectroscopy; TPGS, d-α-tocopherol polyethylene glycol 1000 succinate.
Figure 3
Figure 3
1H NMR spectra of (A) TPGS and (B) TPGS-DTPA synthesized via microwave technology. Abbreviations: DTPA, diethylenetriaminepentaacetic acid; NMR, nuclear magnetic resonance; TPGS, d-α-tocopherol polyethylene glycol 1000 succinate.
Figure 4
Figure 4
13C NMR spectra of (A) TPGS and (B) TPGS-DTPA synthesized via microwave technology. Abbreviations: DTPA, diethylenetriaminepentaacetic acid; NMR, nuclear magnetic resonance; TPGS, d-α-tocopherol polyethylene glycol 1000 succinate.
Figure 5
Figure 5
TEM micrograph of niosomes (N3) at a magnification of 800×. Abbreviation: TEM, transmission electron microscope.
Figure 6
Figure 6
TEM micrograph and measurement of a single niosome (N3) at a magnification of 25,000×. Abbreviation: TEM, transmission electron microscope.
Figure 7
Figure 7
The effect of incubation time on the radiolabeling efficiency of 99mTc-labeled niosomes (N3). Note: Data presented as mean ± SD. Abbreviation: 99mTc, Technetium-99m.
Figure 8
Figure 8
Stability of 99mTc-labeled niosomes (N3) in saline and serum in vitro at 37°C. Note: Data presented as mean ± SD. (n= mean ± SD). Abbreviation: 99mTc, Technetium-99m.
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