Role of chitosan nanoparticles in the oral absorption of Gemcitabine

Gemcitabine is a known cytotoxic agent with a wide spectrum of antitumor activity. It has been employed in therapeutic regimens for various malignancies such as the lung, ovary, breast, and bladder cancers. It also has been used in the treatment of pancreatic cancer, in combination chemotherapy of non-small cell lung cancer (NSCLC) and in leukemia. Its effect results from incorporation into DNA with subsequent inhibition of cell proliferation. Unfortunately, Gemcitabine is rapidly metabolized by the so-called cytidine-deaminase which limits its efficacy. Because of extensive deamination by intestinal cells, its oral administration results in very low bioavailability. The aim of this study was to introduce an oral formulation of the drug for the first time and improve its physicochemical properties. Chitosan nanoparticles containing were produced based on ionic gelation method and tripolyphosphate (TPP). Physicochemical properties such as particle size and shape, loading efficiency and release rate were evaluated. Oral absorption of both free and nanoparticle-loaded drugs was measured using the rat intestinal sac model. The Gemcitabine-loaded chitosan nanoparticles were spherical with a mean size of 95 +/- 8 nm and high drug loading (63%). The nanoparticles showed controlled release pattern characterized by a fast initial release (61%) during the first 8 h, followed by slower and continuous release (74.66%). The absorption study showed that Gemcitabine intestinal transport increased 3-5 folds by loading in chitosan nanocarrier. (C) 2012 Elsevier B.V. All rights reserved.