Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer.

Among the various drug delivery devices, nanoliposome is an emerging formulation in the treatment of cancer. Here we have developed tamoxifen citrate (TC) loaded nanoliposome conjugated with phosphoethanolamine (PE) by thin film hydration method. Various physicochemical and biopharmaceutical characterization studies such as drug-excipients interaction, surface morphology, energy dispersive X-ray analysis, zeta potential, in vitro drug release, cellular uptake, in vitro cytotoxicity assay and in vivo pharmacokinetic profiles were conducted. TC-loaded nanoliposome (TNL1) and PE-conjugated TC-loaded nanoliposome (TNL-PE) showed 3.23±0.26% and 3.07±0.05% drug loading values, respectively. Average diameters (z-average) of the nanoliposomes were within 100 nm, with negative zeta potentials and cumulative percentages of drug release were 75.77±12.21% and 61.04±10.53% at 30 h for TNL1 and TNL-PE respectively. Predominant uptake of both the types of nanoliposomes was visualized in MCF-7 breast cancer cells. TNL1 and TNL-PE decreased the cell viability from 95.95±0.37 to 12.22±0.64% and from 96.51±0.24 to 13.49±0.08% respectively. In vivo pharmacokinetic study showed that AUC 0-∞, AUMC0-∞, MRT, and t1/2 value of TNL-PE increased (22%, 100%, 2.66 fold and 60% respectively) as compared to the free drug. Administration of TNL-PE decreased the renal clearance value (about 38%) as compared to the free drug. TNL1 and TNL-PE released the drug in a sustained manner. Further, TNL-PE may be used for active targeting for breast cancer cells when it is tagged with specific antibodies to PE, a linker molecule.