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 ( 99m Tc) 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.
Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs.
Vitamin E is recognized as an essential vitamin since its discovery in 1922. Most vegetable oils contain a mixture of tocopherols and tocotrienols in the vitamin E composition. Structurally, tocopherols and tocotrienols share a similar chromanol ring and a side chain at the C-2 position. Owing to the three chiral centers in tocopherols, they can appear as eight different stereoisomers. Plant sources of tocopherol are naturally occurring in the form of RRR while synthetic tocopherols are usually in the form of all-racemic mixture. Similarly, with only one chiral center, natural tocotrienols occur as the R-isoform. In this review, we aim to discuss a few chromatographic methods that had been used to separate the stereoisomers of tocopherols and tocotrienols. These methods include high performance liquid chromatography, gas chromatography and combination of both. The review will focus on method development including selection of chiral columns, detection method and choice of elution solvent in the context of separation efficiency, resolution and chiral purity. The applications for separation of enantiomers in vitamin E will also be discussed especially in terms of the distinctive biological potency among the stereoisoforms.
The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.
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