In vivo activity of gemcitabine-loaded PEGylated small unilamellar liposomes against pancreatic cancer

Abstract

Gemcitabine (GEM) is presently the standard option for the treatment of advanced pancreatic cancer (PC). We investigated the in vitro and in vivo antitumor potential of GEM-loaded PEGylated liposomes (L-GEM) as a novel agent for the treatment of PC. In vitro analysis of antitumor activity against human PC cell lines, BXPC-3 and PSN-1, showed a significant time- and dose-dependent reduction of cell viability following exposure to L-GEM as compared to free GEM [at 72 h, IC(50): 0.009 vs. 0.027 microM (P = 0.003) for BXPC-3 and 0.003 vs. 0.009 microM (P < 0.001) for PSN1, respectively]. Confocal laser scanning microscopy demonstrated an effective liposome/cell interaction and internalization process following 3-h cell exposure to L-GEM. The in vivo antitumor activity of L-GEM was investigated in a cohort of SCID mice bearing BxPC-3 or PSN-1 xenografts. Animals were i.p. treated with L-GEM (5 mg/kg), or a threefold increased dose of free GEM (15 mg/kg), or empty liposomes or vehicle, twice a week for 35 days. A significant higher inhibition of tumor growth in mice treated with L-GEM versus free GEM (P = 0.006 and P = 0.004 for BXPC-3 and PSN-1, respectively) or control groups (P = 0.0001), translated in a survival advantage of L-GEM treated animals versus other groups. Pharmacokinetic studies showed enhancement of systemic bioavailability of L-GEM (t (1/2) = 8 h) versus to GEM (t (1/2) = 1.5 h). Our findings demonstrate that L-GEM is an effective agent against PC and exerts higher antitumor activity as compared to free GEM with no appreciable increase in toxicity. These results provide the pre-clinical rational for L-GEM clinical development for the treatment of PC patients.

Novel PEG-coated niosomes based on bola-surfactant as drug carriers for 5-fluorouracil

“…The body weight, feeding behavior and motor activity were used as indicators of general health. The survival rate of xenograft tumour bearing NOD-SCID mice treated with 5-FU-loaded PEG coated bolaniosomes with respect to the free drug was also calculated from the first day of treatment until the day of killing according to an in vivo procedure previously reported (Cosco et al 2009). …”

Gemcitabine-loaded chitosan microspheres. Characterization and biological in vitro evaluation

“…GEM (2′,2′-difluorodeoxycytidine) is a deoxycytidine analogue with a broad spectrum of antitumour activity. It is clinically used in the treatment of several solid tumors, such as ovarian cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, pancreatic and bladder cancer (Heinemann 2003;Bookman 2005;Pauwels et al 2005;Cosco et al 2009). As with the majority of anti-tumoral agents, GEM shows a very low therapeutic index and serious side effects (Barlési et al 2004;Kouroussis et al 2004).…”

Physicochemical features and transfection properties of chitosan/poloxamer 188/poly(D,L-lactide-co-glycolide) nanoplexes

“…The MTT test was performed on the above-mentioned cell lines as previously described 33 to investigate the cytotoxicity of the colloidal formulations. Briefly, the cells were plated in 96-well culture dishes (2×10 4 cells per 0.2 mL), incubated for 24, 48, and 72 hours at 37°C in a humidified atmosphere of 5% CO 2 , and then treated with different concentrations of empty nanoparticles.…”