A new nanomedicine of gemcitabine displays enhanced anticancer activity in sensitive and resistant leukemia types

Reddy, L. Harivardhan; Dubernet, Catherine; Mouelhi, Sinda Lepetre; Marque, Pierre Emmanuel; Desmaële, Didier; Couvreur, Patrick

doi:10.1016/j.jconrel.2007.08.018

Cited by 114 publications

(106 citation statements)

References 17 publications

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“…All treatments induced a significant reduction of the tumor volume compared with saline treated controls. SQdFdC NPs reduced tumor burden by 32% compared with dFdC, confirming the superior activity of squalenoyl gemcitabine nanoparticles, already demonstrated in other animal tumor models [53][54][55]. Interestingly, SQdFdC/SQCKAAKN NPs displayed a greater efficacy in impairing tumor growth compared with SQdFdC NPs (by 40%) and with dFdC (by 60 %) (Fig.…”

Section: Antitumor Efficacy Of Ckaakn-functionalized Nps In Rip-tag2 supporting

confidence: 78%

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Valetti¹,

Maione

Mura

et al. 2014

Journal of Controlled Release

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Chemotherapy for pancreatic cancer is hampered by the tumor physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for the therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanism of action. Graphical abstract

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Section: Antitumor Efficacy Of Ckaakn-functionalized Nps In Rip-tag2 supporting

confidence: 78%

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Valetti¹,

Maione

Mura

et al. 2014

Journal of Controlled Release

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“…72 In addition to storage, a gradual cleavage of Sq-gemcitabine in native and active form also explains his efficiency. Cathepsin B, a lysosomal enzyme often overexpressed in cancer cells, 72 …”

Section: Squalenoylationmentioning

confidence: 99%

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

2012

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Gemcitabine, an anticancer agent which acts against a wide range of solid tumors, is known to be rapidly deaminated in blood to the inactive metabolite 2',2'-difluorodeoxyuridine and to be rapidly excreted by the urine. Moreover, many cancers develop resistance against this drug, such as loss of transporters and kinases responsible for the first phosphorylation step. To increase its therapeutic levels, gemcitabine is administered at high dose (1000mg/m²) causing sides effects (neutropenia, nausea…).To improve its metabolic stability, its cytotoxic activity and to

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“…At room temperature, the particles are in the solid state, therefore the mobility of incorporated drugs is reduced, which is prerequisite for controlled drug release. They have potential to incorporate lipophilic or hydrophilic drugs or diagnostics (Muhlen et al, 1998;Utreja & Jain, 2002;Reddy et al, 2007). Intravenous studies show that liver is the major organ depot for nanoparticles followed by spleen for particles in the size range of 200-300 nm (Garnett & Kallinteri, 2006;De Jong et al, 2008;Sarlo et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles

Doijad

Shivakumar

et al. 2013

Drug Delivery

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Gemcitabine-loaded solid lipid nanoparticles (SLNs) were produced by double emulsification technique using stearic acid as lipid, soy lecithin as surfactant and sodium taurocholate as cosurfactant. Prepared nanoparticles are characterized for particle size and surface morphology using scanning electron microscopy (SEM). Particle yield, entrapment efficiency and zeta potential were also determined. In-vitro release studies were performed in phosphate-buffered saline (PBS) pH 7.4 using metabolic shaker. The formulation F6 with maximum entrapment efficiency 72.42% and satisfactory in-vitro release was selected. In-vivo tissue distribution to liver, spleen, lung, heart and kidneys of optimized formulation followed by stability study under specific conditions were also determined. This investigation has shown preferential drug targeting to liver followed by spleen, lungs, kidneys and heart. Stability studies showed no significant change in the particle size followed with very slight decrease in entrapment efficiency at 25 AE 2 C/60 AE 5% RH over a period of three months.

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A new nanomedicine of gemcitabine displays enhanced anticancer activity in sensitive and resistant leukemia types

Cited by 114 publications

References 17 publications

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles

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