The conventional chemotherapies have minimal or spared effect on cancer stem cells, which are now considered to be a reason for chemotherapy resistance, relapse and metastasis. Breast cancer stem cells (BCSCs) were not only reported to be resistant to conventional therapies but were also found to increase in proportion after treatment. Gene profiling of BCSCs revealed overexpression of CXCR1, a receptor for cytokine IL-8. Reparixin a non-competitive allosteric inhibitor of CXCR1, blocks the intracellular signal transduction events activated by binding of IL8 to CXCR1 and selectively eliminates the BCSCs. However, its highly hydrophobic nature induces delivery challenges and its poor pharmacokinetic profile restricts it anti-CSCs potentials. Further RPX was found to be less effective against the non-CSCs or bulk tumor cells, so it has to be combined with another conventional anti-cancer drug to ensure complete removal of all tumor cells. In this thesis, I focused on the development and evaluation of single and composite (2-in-1) drug-loaded polymeric micelles (PMs) of reparixin (RPX, a potent CXCR1 antagonist) and paclitaxel (PTX) to target both BCSCs (CXCR1+ and ALDHFLUOR+) and bulk tumor cells, respectively. This is the first study to look into the effectiveness of RPX and PTX PMs combination in decreasing the stemness (self-renewal and differentiation) and viability of CSCs. The PMs were prepared with poly(ethylene glycol)-block-poly(D,L-lactic acid) using the lyophilization technique. We have specifically tested the efficacy of these polymeric micelles in decreasing the viability and stemness of BCSCs. The composite PMs efficiently decreased viability in both unsorted and sorted CXCR1+ cells, whereas RPX-PMs induced significant viability loss only in the sorted CXCR1+ BCSCs. Flow cytometric analysis indicated 2.7- and a 5-fold decrease in CXCR1+ and ALDHFLUOR+ BCSCs in cell cultures after treatment with composite PMs, respectively. As confirmed by a decrease in mammosphere forming capability and increased confidence interval of 1 CSCs per 250 cells, treatment with composite PMs decreased the stemness of HCC-1954 breast cancer cell cultures. The treatment with the combination of PTX-PMs (25 nM) and RPX-PMs (>25 nM) for 3days, produced a significantly higher cytotoxic effect on CXCR1+ cells in comparison to the PTX-PMs alone. Whereas, enhancing the RPX-PMs concentration were not able to induce major cytotoxicity effect in unsorted and CXCR1- cancer cell. Interestingly, 2-in-1 PMs treated cultured showed lowering of CXCR1+ cells irrespective of the increase in IL-8 levels, confirming their ability to block CXCR1 even in the presence of higher IL-8 levels. These micelles activated FAK/AKT/FOXO3A pathway, which enhanced FasL levels in cultures, leading to the killing of bulk tumor or CXCR1- cells by a bystander effect. Drugs encapsulation in PMs enhanced the pharmacokinetic profile of both drug, with enhanced AUC, Cmax and reduced volume of distribution. The 4 weeks combination therapy with weekly administration of 2-in-1PMs and alternate day administration of RPX-PMs decreased both tumor size and the BCSCs number in the residual tumors. The study suggested the use of higher dose or prolonged treatment with RPX-PMs along with 2-in-1 PMs or PTX-PMs could provide a superior anti-cancer effect by simultaneously eliminating both CSSs and bulk tumor cells in breast cancer.