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Creating ‘Smart’ Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers

R.M. Sawant, J.P. Hurley, S. Salmaso, A. Kale, E. Tolcheva, T.S. Levchenko and V.P. Torchilin
Northeastern University, US

Keywords:
pH responsive, polymeric micelles, liposomes, TATp

Abstract:
Double targeted nanocarriers (liposomes and micelle) were prepared by combining on their surface cell-penetrating TAT peptide (TATp) and pH-sensitive PEG-PE (mPEG-Hz-PE). The pH-sensitive PEG-PE polymer degraded at acidic pH by cleaving off of the hydrazone bond between PEG and PE. Fuorescently-labeled pH-sensitive TATp containing nanocarriers were prepared and incubated at different pH (pH 7.4 and pH 5) and then interacted with mouse fibroblast or astrocytoma cells. The extent of interaction was monitored from the fluorescence assciated with the cells. Incresed fluorescence was observed in cases where the carriers were treated at pH 5. This indicated that mPEG-Hz-PE successfully shielded the TATp when at pH 7.4, which resulted in a minimal interaction of carrier with the cell via the TATp function; however the preincubation of the preparations at pH 5 resulted in the detachment of the shielding PEG function, exposure of the TATp function, and effective interaction with cells.

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