Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer

Кузнецова, Н. В.; Sevrin, Chantal; Lespineux, David; Bovin, Nicolai V.; Водовозова, Е. Л.; Mészáros, Tamás; Szebeni, János; Grandfils, Christian

doi:10.1016/j.jconrel.2011.12.010

Cited by 100 publications

(88 citation statements)

References 45 publications

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“…16 Empty liposomes were composed of PC-PI, 9:1. Briefly, dry lipid films were hydrated in phosphate-buffered saline (PBS: 1.5 mM KH 2 PO 4 , 1.1 mM NaH 2 PO 4 • 2H 2 O, 6.3 mM Na 2 HPO 4 , 2.7 mM KCl, and 136.8 mM NaCl) containing 1 mM EDTA, pH 7.0, and subjected to 6-10 cycles of freezing/thawing (liquid nitrogen/+40°C).…”

Section: Liposome Preparation and Characterizationmentioning

confidence: 99%

“…The liposomes are stable in buffer for at least 3 weeks; even after freezing, thawing, and ultrasonic treatment, they retain the prodrug in the lipid bilayer. 14,16 In a panel of in vitro tests, overall, the formulation showed good hemotolerance. 16 The liposomal formulation of MTX-DG (MTX-DG liposomes) successfully surmounted the resistance of cultured RFC-deficient human T-lymphoblastic cells toward MTX.…”

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confidence: 98%

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Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Алексеева¹,

Моисеева²,

Onishchenko³

et al. 2017

IJN

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In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5–2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX.

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Section: Liposome Preparation and Characterizationmentioning

confidence: 99%

mentioning

confidence: 98%

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Алексеева¹,

Моисеева²,

Onishchenko³

et al. 2017

IJN

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show abstract

“…Therefore, the main source of hemolysis might be the effects that the drug moiety produces on the NP surface or when encapsulated on it. Indeed, it was recently reported that MTX incorporated in liposomal formulations displayed higher hemoreactivity than its free solution [47]. The agglutination induced by the NPs at the highest concentration tested may be caused by increased binding of the NPs to the erythrocyte membrane, which might deformed cells and hence decrease the repulsion among them [48].…”

Section: Discussionmentioning

confidence: 95%

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

et al. 2013

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Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from N α ,N ε -dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy.

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“…Characterization and physical stability analysis of ALA-NLC Size of lipid nanoparticles has been considered as one of qualitative parameters affecting their reactivity in natural surroundings even if there is no predictable regulation on whether smaller or bigger size is desirable for circulating nanoparticles as for their reactivity with complement (Kuznetsova et al, 2012). The ALA-NLC dispersed in deionized water was 149.7 AE 5.4 nm.…”

Section: Resultsmentioning

confidence: 99%

Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cellsin vitro

Wang

Xia²

2013

Drug Delivery

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ALA-loaded nanostructured lipid carrier (ALA-NLC) was designed to improve physicochemical stability and water solubility, and promote sustained release of ALA as well as determine the biocompatibility of ALA-NLC. The ALA-NLC manufactured using hot high-pressure homogenization technique was investigated in terms of size, zeta potential, FTIR analysis and release behavior. In vitro cytotoxicity and biocompatibility were determined by incubating with HaCaT cells using the MTT assay, HE staining and Hoechst 33342 staining. Cell behavior and cellular division of HaCaT cells untreated and treated by ALA-NLC were investigated in real-time images gathered using time-lapse imaging system. The release investigation illustrated that only 6.9% of ALA released in 30 min from ALA-NLC formation, whereas it was 30.3% in free ALA system. ALA-NLC possessed a satisfactory release behavior of sustained release up to 72 h. It showed that ALA-NLC did not exert hazardous effect on HaCaT cells up to 81.9 mg/L without morphological alterations, revealing a satisfactory biocompatibility. Evidence was provided from time-lapse imaging system that cell behavior and cellular division of ALA-NLC treated HaCaT cells were in accordance with the control. These results of this investigation demonstrated that NLC encapsulated ALA formation (ALA-NLC) can improve stability, solubility and release of ALA; ALA-NLC was biocompatible to HaCaT cells.

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Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer

Cited by 100 publications

References 45 publications

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cellsin vitro

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