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

Luisa Vicari¹ , Teresa Musumeci² , Ignazio Giannone² , Luana Adamo¹ , Concetta Conticello¹ , Ruggero De Maria¹^,4 , Rosario Pignatello² , Giovanni Puglisi² and Massimo Gulisano¹^,3^,5

¹Dipartimento di Oncologia Sperimentale, Istituto Oncologico del Mediterraneo, Viagrande (CT), Italy

²Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Catania, Italy

³IOM Ricerca S.r.l., Viagrande (CT), Italy

⁴Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Roma, Italy

⁵Dipartimento di Scienze Fisiologiche, Università degli Studi di Catania, Catania, Italy

author email corresponding author email

BMC Cancer 2008, 8:212doi:10.1186/1471-2407-8-212


Published:	25 July 2008

Abstract

Background

PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor^®EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.

Methods

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.

Results

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.

Conclusion

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.