Liposomal delivery improves the growth-inhibitory and apoptotic activity of low doses of gemcitabine in multiple myeloma cancer cells

Celia, Christian; Malara, Natalia; Terracciano, Rosa; Cosco, Donato; Paolino, Donatella; Fresta, Massimo; Savino, Rocco

doi:10.1016/j.nano.2008.02.003

Cited by 51 publications

(36 citation statements)

References 57 publications

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“…The results suggest that the shelf stability of formulation could further be improved by selecting an appropriate containerclosure system impermeable to the seepage of moisture into the lyophilized product at high humidity conditions. Cellular uptake and cytotoxicity of gemcitabine were significantly higher using gemcitabine-loaded nanoparticles compared to GEMCITE® which is in coherence with the previous studies [5,13,27,37]. Several endocytosis pathways have been reported for the uptake of nanoparticles by the cancer cells such as clathrin-mediated endocytosis, caveolaemediated endocytosis, and clathrin and caveolae-independent endocytosis and macropinocytosis [38].…”

Section: Discussionsupporting

confidence: 89%

“…However, its clinical benefit is only modest due to its rapid metabolism in the plasma resulting in its inactive metabolite thereby necessitating the use of higher dose for effective treatment. To overcome such problems, several delivery approaches for gemcitabine have been tried which include liposomes [2][3][4][5][6][7], nanoparticles [7][8][9][10][11][12][13][14], carbon nanotubes [15], lipidic/ nonlipidic conjugates [16], and polymeric drug conjugates [17][18][19]. Liposomes provide an inner aqueous core for efficient loading of hydrophilic drugs like gemcitabine and showed improved growth inhibitory activity in cancer cell lines [2,5] and efficacy in animal models [6].…”

Section: Introductionmentioning

confidence: 99%

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Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation

Mittal

Mahato

Kumar

2014

Drug Deliv. and Transl. Res.

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Core-shell nanoparticulate formulation of gemcitabine was prepared by incorporating gemcitabine in a hydrophilic bovine serum albumin (BSA) core surrounded by hydrophobic poly(DL-lactic acid-co-glycolic acid) (PLGA) shell with a particle size of 243 nm and encapsulation efficiency of 40.5 %. Prepared formulations were lyophilized, wherein several cryoprotectants were screened for product attributes such as cake appearance, reconstitution with water, and size constancy. Trehalose was screened as a lyoprotectant, which showed stability for 6 months at 5 °C and 25 °C/60 % relative humidity (RH) conditions. However, an increase in particle size was observed at accelerated conditions (40 °C/75 % RH). In vitro evaluation of these nano-formulations in MCF-7 breast cancer cells showed enhanced cellular uptake (90 %) as compared to GEMCITE® uptake (51 %) in 6 h along with reduced IC50 value at 72 h (16 μM versus 30 μM). In vivo studies in Sprague Dawley rats showed C max, t 1/2, and area under the curve (AUC) at 2.55 μg/ml, 13.6 h, and 28,322.5 μg/l/h, respectively, whereas GEMCITE® at the same dose showed significantly lower corresponding values at 1.94 μg/ml, 6.89 h, and 13,967 μg/l/h. In the same study, AUC and C max of inactive metabolite of gemcitabine (dFdU) were reduced by 33 and 42 %, respectively, for these nanoparticles compared to GEMCITE®. In 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model, significantly reduced tumor growth was observed in gemcitabine-loaded-nanoparticle-treated animals compared with GEMCITE®-treated animal at equivalent dose (121 versus 243 % in 30 days). The results indicated that our core-shell nanoparticles are more effective for tumor reduction compared to marketed formulation of gemcitabine, GEMCITE®.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation

Mittal

Mahato

Kumar

2014

Drug Deliv. and Transl. Res.

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“…Our research group has demonstrated that liposomal encapsulation increases the antitumoral efficacy of GEM as a consequence of an increased intracellular accumulation in different cancer cell lines (Celia et al 2008b;Cosco et al 2009a), while the similar cytotoxic effect obtained by using free PTX and PTX-loaded liposomes was in agreement with the findings reported by Crosasso et al (2000).…”

Section: Evaluation Of Cytotoxicitysupporting

confidence: 89%

Liposomes as multicompartmental carriers for multidrug delivery in anticancer chemotherapy

Cosco

Paolino

Maiuolo

et al. 2010

Drug Deliv. and Transl. Res.

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A new PEGylated liposomal formulation containing both gemcitabine (GEM) and paclitaxel (PTX) was investigated in order to realize an innovative multidrug carrier (MDC) to test on human cancer cells. The MDC in question was realized by the liposome extrusion method. Photocorrelation spectroscopy was used for the physicochemical characterization of the vesicular carriers. In vitro cytotoxicity was studied through MTT testing. The contemporary presence of the two antitumoral compounds induced no destabilization phenomena in the liposomal structure. The extrusion method provided vesicles with mean sizes of ∼100 nm and a zeta-potential of ∼ -10 mV. The liposomal MDC showed a high drug loading capacity (∼90% and ∼80% for GEM and PTX, respectively) as well as a controlled release of the active compounds over a 24-h period. Cell viability testing on Michigan Cancer Foundation-7 human breast cancer cells evidenced the MDC as having a stronger cytotoxic effect with respect to the active compounds tested in free and liposomal formulations, both as single molecules and in association. Flow cytometry furnished evidence of the synergistic in vitro antitumoral action between the GEM and PTX co-encapsulated the liposomal MDC. This formulation may offer even more advantages in in vivo testing in terms of drug pharmacokinetic, biodistribution, and antitumoral efficacy for the treatment of breast cancer, as compared to past formulations.

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“…Recent investigations on gemcitabine-loaded liposomes have demonstrated that the liposomal carriers can improve the in vitro and in vivo anticancer activity of this compound against different antitumoral cell lines [35,40,41]. Positive results in terms of an antiproliferative effect were also recently observed in the case of gemcitabine-loaded supramolecular vesicular aggregates [8].…”

Section: In Vitro Anticancer Activitymentioning

confidence: 99%

Folate-targeted supramolecular vesicular aggregates based on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs

Licciardi¹,

Paolino²,

Celia³

et al. 2010

Biomaterials

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Liposomal delivery improves the growth-inhibitory and apoptotic activity of low doses of gemcitabine in multiple myeloma cancer cells

Cited by 51 publications

References 57 publications

Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation

Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation

Liposomes as multicompartmental carriers for multidrug delivery in anticancer chemotherapy

Folate-targeted supramolecular vesicular aggregates based on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs

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