Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer.
2016
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-∞ , AUMC 0-∞ , 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.
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