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. 2016 Jan-Apr;15(1):7-11.
doi: 10.4103/1450-1147.167594.

Nanotamoxifen Delivery System: Toxicity Assessment After Oral Administration and Biodistribution Study After Intravenous Delivery of Radiolabeled Nanotamoxifen

Jaya Shukla  1 , Amit Kumar Dinda  2 , Abhay Krishna Srivastava  3 , Kamna Srivastava  4 , Bhagwant Rai Mittal  1 , Guru Pad Bandopadhyaya  5
Affiliations

Nanotamoxifen Delivery System: Toxicity Assessment After Oral Administration and Biodistribution Study After Intravenous Delivery of Radiolabeled Nanotamoxifen

Jaya Shukla et al. World J Nucl Med. 2016 Jan-Apr.

Abstract

Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m ((99m)Tc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.

Keywords: Biodistribution; delivery system; free radical formation; nanotamoxifen; oral dose; radiolabeling; toxicity.

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Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
(a) Histogram showing average ± S.D (n = 3) of cre, bil, alb, glob, tp, ua per dose group (D1 = 5 μg, D2 = 30 μg, D3 = 200 μg) for 15 days (-1) and 30 days (-2) of exposure to oral nanotamoxifen (b) Histogram showing average ± S.D (n = 3) of serum glutamic oxaloacetic transaminase (SGOT) or AST, serum glutamic-pyruvic transaminase (SGPT) or ALT, ALP, tc, urea per dose group D1 = 5 μg, D2 = 30 μg, D3 = 200 μg) for 15 days (-1) and 30 days (-2) exposure to oral nanotamoxifen
Figure 2
Figure 2
Gamma camera images of Albino wistar rats after Tc-99m-nanotamoxifen injection from tail vein. (a) 15 min, (b) 1hr, (c) 3hr post intravenous injection. B-blood, Bo-bone, M-muscle
Figure 3
Figure 3
99mTc-nanotamoxifen-organ distribution (3 h post injection) in albino Wistar rats
See this image and copyright information in PMC

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