Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.PTX is a taxane plant product derived from the bark of the pacific yew tree Taxus brevifolia. Unlike other tubulin binding agents, such as Vinca alkaloids, which induce the disassembly of microtubules, PTX promotes the stabilization of tubulin polymerization [1]. The microtubule formed in the presence of PTX are extremely stable and dysfunctional with a consequent cell cycle arrest at the G2/M phase and inhibition of mitosis [2].PTX has a significant antineoplastic activity in solid tumor and it is currently approved by both the FDA and the EMEA for the treatment of non-small cell lung cancer, breast cancer, ovarian cancer and AIDS-related Kaposi's sarcoma. In addition PTX is also successfully used, either as single agent and in combination with other antineoplastic agents, in the treatment of thyroid, bladder, head and neck cancers [3-8].However, the clinical application of PTX is limited by its low therapeutic index and its low solubility in water [9]. Accordingly, standard formulation of PTX (Taxol？) requires the use of solvents, such as Cremophor？ EL (polyoxyethylated castor oil) and dehydrated alcohol, which contribute to most of