A Comparative Evaluation of Anti-Tumour Activity Following Oral And Intravenous Delivery of Doxorubicin In A Xenograft Model of Breast Tumour

Extensive studies have been conducted on natural materials due to their unique and biodegradable properties for oral drug delivery. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral drug delivery system. NaCNs was explored to improve the therapeutic potential of Doxorubicin (DOX) with reduced toxicity in healthy organs. The synthesized and thoroughly characterized DOX-loaded NaCNs were subjected to in vivo anti-tumour evaluation and bio-distribution analysis in a 4T1-induced breast cancer model. Our findings indicated an almost eight-fold reduction in tumour size in the group orally treated with DOX-NaCNs when compared to free DOX. It is plausible that the enhanced anti-tumour effects of oral DOX-NaCNs is related to the controlled release of DOX from the delivery system as well as the longer circulatory time of the drug in the blood, as confirmed by the bio-distribution study, when compared with free DOX and the intravenous formulation of DOX-NaCNs. Additionally, the tumour drug accumulation for the orally administered DOX-NaCNs was 1.27- and 6.8-fold higher than that of the intravenously administered DOX-NaCNs and free DOX, respectively and overall, was 8.34-times higher than the orally administered free DOX. In comparison, the orally administered DOX-NaCNs showed significant reduction in tumour size (5.66 ± 4.36mm3) after the two doses as compared to intravenously administered DOX-NaCNs (10.29 ± 4.86 mm3) on day 17 of the experimental period. Moreover, NaCNs were well tolerated in the mice at a single dose of 2,000 mg/kg in an acute oral toxicity study. Moreover, no significant change in the body weight was observed after treatment with the single dose of NaCNs when compared to the control group. Thus, NaCNs emerge as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumour effects that present as a potential option for oral chemotherapy.