Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate

The purpose of this study was to develop a novel lectin-conjugated isopropyl myristate (IPM)-incorporated PLGA nanoparticle system (NP) for the local delivery of paclitaxel to the lungs. neat germ agglutinin (WGA) was conjugated onto preformed IPM- and paclitaxel-loaded PLGA NPs by a two-step carbodiimide method following comparative uptake studies of Concanavalin A, Ricinus communis-120 and WGA on A549, H1299 and CCL-186 cells. WIT-NP with mean diameter of 33 1 rim and zeta potential of -4.3 mV were prepared with yield of 66% and paclitaxel encapsulation efficiency of 61%. Particle size was expanded by surface conjugation with WGA, while zeta potential was reduced by the addition of IPM and WGA. In vitro paclitaxel release profile was not affected by WGA but initial drug release was enhanced by adding IPM into the formulation. The WIT-NP showed a burst-release of about 32% of the paclitaxel load within the first 5 h followed by a slow zero-order release of another 7% of the drug load in the next 115 h. Compared with the clinical paclitaxel formulation, paclitaxel-loaded nanoparticles without IPM or WGA, or paclitaxel-loaded nanoparticles with only IPM or WGA, the WIT-NP had superior in vitro cytotoxicity against A549 and H 1299 cells. IC50 for WIT-NP after 5 and 24 h incubation with A549 cells were not significantly different (15.5 and 15 mu M, respectively) whereas the clinical formulation was not cytotoxic after 5 h but had IC50 of 14 mu M after 24 h incubation. WIT-NP exhibited stronger cell-killing effect because of more efficient cellular uptake via WGA-receptor-mediated endocytosis and IPM-facilitated release of paclitaxel from the NPs. (c) 2005 Elsevier B.V. All rights reserved.