Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines

We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH₂ (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160–477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140–250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX > DOX > 5-FU > GEM > DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC₅₀ values.