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Uptake and Transport of Novel Amphiphilic Polyelectrolyte-Insulin Nanocomplexes by Caco-2 Cells—Towards Oral Insulin

Uptake and Transport of Novel Amphiphilic Polyelectrolyte-Insulin Nanocomplexes by Caco-2 Cells—Towards Oral Insulin,10.1007/s11095-010-0345-x,Pharmac

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Uptake and Transport of Novel Amphiphilic Polyelectrolyte-Insulin Nanocomplexes by Caco-2 Cells—Towards Oral Insulin   (Citations: 1)
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Purpose  The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method  Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine, and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake was investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER), and insulin transport across the monolayers was determined. Result  Pa and insulin were co-localised in cell membranes, while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly, and insulin transport through monolayers increased when QPa or Pa was used. Conclusion  These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.
Journal: Pharmaceutical Research - PHARMACEUT RES , vol. 28, no. 4, pp. 886-896, 2011
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