Assessment of Anti-Carcinogenic Potential of Neem (<i>Azadirachta indica</i>) Leaf Extract Loaded Calcium Phosphate Nanoparticles against Experimentally Induced Mammary Carcinogenesis in Rats

Considering the need for alternative medicine in alleviation of tumors and use of nanotechnology in furthering the action of herbal/natural products, the present study was designed to evaluate the anti-carcinogenic potential of Neem leaf Extract (NE) loaded calcium phosphate nanoparticles (NE-CaNP) on 7, 12-Dimethylbenzanthracene (DMBA) induced mammary tumors in female Sprague-Dawley rats. Ultrastructurally, the NE-CaNP were smooth, spherical with a tendency to agglomerate and evenly distributed. The NE-CaNP had a mean diameter of 231.4 ± 89.2 nm and zeta potential of -31.3mV. The mean coupling efficiency of CaNP was 90-91 %. The experimental trial consisted of control, NE-CaNP control, DMBA, DMBA+NE and DMBA+NE-CaNP groups. The mean latency periods for occurrence of mammary tumor were significantly (P ≤ 0.05) increased in the DMBA+NE and DMBA+NE-CaNP groups compared to the DMBA group. The mean latency period in the DMBA+NE-CaNP group was significantly (P ≤ 0.05) higher than the DMBA+NE group. The mean tumor frequency, volume and weight were significantly (P ≤ 0.05) decreased in the DMBA+NE-CaNP group. Histopathologically, the number of benign lesions was found highest (47.54%) in DMBA+NE-CaNP group rats. The relative percent reduction in malignancy as compared to the DMBA group was 42.86% and 54.29% in the DMBA+NE and DMBA+NE-CaNP groups respectively. In conclusion, the neem leaf extract loaded calcium phosphate nanoparticles were found to have better anti-carcinogenic potential by significantly reducing the incidence, frequency, weight, volume, malignancy and increased the tumor latency period of DMBA induced mammary tumors in female Sprague-Dawley rats as compared to rats treated with neem extract alone. Findings of the present study suggested that the neem leaf extract loaded calcium phosphate nanoparticles (NE-CaNP) has immense anticancer potential in terms of reduction in tumor burden and malignancy.