A comparative evaluation of anti-tumor activity following oral and intravenous delivery of doxorubicin in a xenograft model of breast tumor

Rehan Farah; Emranul Karim Md.; Ahemad Nafees; Farooq Shaikh Mohd.; Gupta Manish; Gan Siew Hua; Chowdhury Ezharul Hoque

doi:10.1007/s40005-022-00595-7

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자료유형: 학술저널

저자정보: Rehan Farah (Monash University Malaysia Malaysia) Emranul Karim Md. (Monash University Malaysia Malaysia) Ahemad Nafees (Monash University Malaysia Malaysia) Farooq Shaikh Mohd. (Monash University Malaysia Malaysia) Gupta Manish (Monash University Malaysia Malaysia) Gan Siew Hua (Monash University Malaysia Malaysia) Chowdhury Ezharul Hoque (Monash University Malaysia Malaysia)

저널정보: 한국약제학회 Journal of Pharmaceutical Investigation Journal of Pharmaceutical Investigation 제52권 제6호

발행연도: 2022.11

수록면: 787 - 804 (18page)

DOI: 10.1007/s40005-022-00595-7

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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.

#Casein #Oral drug delivery #Breast cancer #Doxorubicin #Biodistribution studies

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