In Vitro Evaluation of the Activity of Gemcitabine-Loaded Pegylated Unilamellar Liposomes Against Papillary Thyroid Cancer Cells~!2010-04-18~!2010-06-27~!2010-08-23~!

Abstract

Papillary carcinoma is the most common form of malignant thyroid tumor. At present, a subset of these tumors are poorly responsive to the current treatment. Gemcitabine is a pyrimidine analog active against different types of solid tumors, but its use is limited by its short half-life. To improve the therapeutic effectiveness of this drug, gemcitabineloaded unilamellar pegylated liposomes were prepared and investigated against two human papillary thyroid carcinoma cell lines, i.e. TPC-1 and B-CPAP cells. The pH gradient drug encapsulation followed by the membrane extrusion technique were used to achieve unilamellar liposomes characterized by a mean size of ~200 nm, a polydispersity index of 0.02 and a zeta potential of-1.7 mV. The gemcitabine was released from liposomes following a biphasic profile. The liposomal encapsulated gemcitabine showed an increased cytotoxic activity compared to the free drug against both thyroid carcinoma cell lines, as a consequence of the better drug internalization favored by the vesicular device. These findings demonstrate the advantage of channeling gemcitabine by liposomes suggesting a promising role for such a pharmaceutical formulation in the treatment of refractory papillary thyroid carcinoma.

Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives

“…21,54 Similar experiments were performed using other types of thyroid cancer cell lines (TPC-1, B-CPAP) with the aim of obtaining further evidence that the liposomal PEGylated formulation increases cellular uptake of gemcitabine and consequently amplifies its pharmacological effect. 51 This was confirmed by confocal laser scanning microscopy (CLSM); after 6 hours of incubation with fluorescein-labeled PEGylated liposomes, dissemination of the colloid was observed in all cellular compartments of the B-CPAP cells, including the cell membrane and cytoplasm, thus demonstrating internalization of the colloid ( Figure 6).…”

“…36 This research showed that the PEGylated liposomal formulation had greater cytotoxic activity (evaluated as a function of drug concentration following 48 hours of incubation) than the free form of the drug, probably because encapsulation of the antitumoral compound in a liposomal system enabled greater intracellular uptake due to the ability of the vesicles to penetrate the cell membrane by fusion or endocytotic mechanisms. 11,51 Free gemcitabine did not have significant cytotoxic effects on the colon carcinoma cells at any of the experimental drug concentrations, while the liposomal formulation showed high antitumoral efficacy even at low drug concentrations. 36 Electrostatic charge and the presence of PEG moieties on the liposomal surface were the most important factors influencing interaction between the vesicular structures and the biological membranes.…”

How can nanomedicines overcome cellular-based anticancer drug resistance?

“…170 For instance, a superior anticancer activity of PEGylated liposomal formulations of gemcitabine over the free drug was observed in various cancer cell lines in vitro. [171][172][173][174] The cytotoxicity of the formulation was evident after 12 h and 24 h of incubation whereas both higher drug concentrations and longer post-incubation times were needed to achieve a pharmacological effect with the free gemcitabine. This result was likely due to an improvement in cellular uptake of the drug which was confirmed by HPLC analysis and confocal laser scanning microscopy.…”