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KMID : 1146920220520060787
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 6 p.787 ~ p.804
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A comparative evaluation of anti-tumor activity following oral and intravenous delivery of doxorubicin in a xenograft model of breast tumor
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Rehan Farah
Karim Md. Emranul
Ahemad Nafees
Shaikh Mohd. Farooq
Gupta Manish
Gan Siew Hua
Chowdhury Ezharul Hoque
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Abstract
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Purpose: Natural materials have been extensively studied for oral drug delivery due to their biodegradability and other unique properties. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral delivery system that would improve the therapeutic potential of doxorubicin (DOX) and reduce its toxicity.
Methods: DOX-loaded NaCNs were synthesized and thoroughly characterized, then subjected to in vivo anti-tumor evaluation and bio-distribution analysis in a 4T1-induced breast cancer model.
Results: Our findings indicated that the tumor would shrink by eight-fold in the group orally treated with DOX-NaCNs when compared to free DOX. The tumor accumulated drug 1.27-fold more from the orally administered DOX-NaCNs compared to the intravenously administered DOX-NaCNs, 6.8-fold more compared to free DOX, and 8.34-times more compared to orally administered free DOX. In comparison, the orally administered DOX-NaCNs lead to a significant reduction in tumor size (5.66?±?4.36 mm3) compared to intravenously administered DOX-NaCNs (10.29?±?4.86 mm3) on day 17 of the experiment. NaCNs were well tolerated at a single dose of 2000 mg/kg in an acute oral toxicity study.
Conclusion: The enhanced anti-tumor effects of oral DOX-NaCNs might be related to the controlled release of DOX from the delivery system when compared to free DOX and the intravenous formulation of DOX-NaCNs. Moreover, NaCNs is recognized as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumor effects that has a potential for oral chemotherapy.
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KEYWORD
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Casein, Oral drug delivery, Breast cancer, Doxorubicin, Biodistribution studies
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