Development of Ligand Conjugated Nano Drug Delivery System to Prevent Lymphatic Metastasis of Breast Cancer

Abstract

In the present scenario there are sufficient amount of anticancer drugs which can kill the tumor cells in the body. But, these drugs are equally toxic to the healthy cells of the body and cause several potential side effects, leading to reduced patient life and compliance. To avoid the possible side effects posed by the anticancer drugs, many people prefer surgical and radiation methods for the treatment. Though surgical removal of the tumor in breast cancer patients has been found to be beneficial, the incidence of recurrence of cancer to the other parts of the body (including breast) is very high and is attributed to metastasis of the cancer cells from the primary site through regional lymphatics. As metastasis of cancerous cells occurs in the regional lymphatics, it is essential for the drug to reach the regional lymphatics to arrest metastasis. In order to reach the lymphatics, the size of the particles should be in the range of 10- 100 nm, the uptake rate into the lymphatics should be high and the delivery route should be appropriate. Solid lipid nanoparticles (SLNs) can safely target and deliver anticancer drugs by subcutaneous administration to the regional lymphatics, the residing place of the metastatic cancer cells. Hence, the current doctoral research work has been planned to work on the development and evaluation of ligand conjugated SLNs of Imatinib mesylate (IM) which can specifically target and kill the tumor cells in the lymphatics. The development of SLNs requires solubilisation of the drug in the lipid carrier to achieve good entrapment efficiencies and stability. There is no model to predict the solubility of drugs in lipids. Hence, examining the various properties of lipids which influence their ability to solubilise the drugs has also been examined and a model has been developed to predict the solubility of IM in lipids for the first time. The utility of quillaja saponin (QS), a natural surfactant obtained from the bark of Quillaja saponaria, in the preparation of SLNs has also been evaluated for the first time.