Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing water-soluble prodrugs of paclitaxel

Ceruti, Maurizio; Crosasso, Paola; Brusa, Paola; Berlier, Gloria; Dosio, Franco; Cattel, Luigi

doi:10.1016/s0168-3659(99)00198-4

Cited by 75 publications

(41 citation statements)

References 45 publications

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“…Our findings suggest that compounds that regulate the polymerization states of microtubules may be used to enhance transfection efficiency by preventing liposome-DNA complexes from degrading in lysosomes. In addition, microtubule inhibitors such as vincristine, 15,16 and microtubule stabilizers such as taxol, 17 are often used in the treatment of cancer, although the effective concentration of these substances often overlaps their toxic dose range. Since it has been reported that encapsulation of these drugs in liposomes is an effective way to reduce their toxicity, [15][16][17][18] gene delivery using liposomes in the presence of such drugs to treat cancer might be a powerful technique due to the dual effects of gene therapy and chemotherapy.…”

Section: Figure 4 Effects Of Nocodazole and Taxol On The Distributionmentioning

confidence: 99%

Microtubule involvement in the intracellular dynamics for gene transfection mediated by cationic liposomes

2001

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7 To improve the efficiency of the transfection, it is essential to elucidate the mechanism not only as to how exogenous DNA is taken up and transported to the nucleus, but also how DNA degrades, since inhibition of the degradation of exogenous DNA could contribute to the enhancement of transfection efficiency, as well as facilitation of the nuclear translocation. Liposome-DNA complex is taken up by endocytosis, and the internalized DNA is released from endosomes by their acidification. [8][9][10] However, the details of intracellular events during lipofection are still unknown. Although many lines of evidence suggest that microtubules are responsible for the intracellular trafficking of materials internalized by endocytosis, 11,12 no direct observation as to how microtubules are involved in the intracellular dynamics of exogenous liposome-DNA complex has been reported. In the present study, therefore, we undertook simultaneous visualization of lipo- some-DNA complexes and microtubules in living cultured cells, and showed that microtubules are involved in the intracellular transport of the exogenous liposome-DNA complex.In order to investigate the contribution of microtubules to the transport of exogenous DNA and liposomes, we tested the effects of nocodazole and taxol on transfection efficiency in COS-7 cells by luciferase assay. For transfection with luciferase plasmids using cationic lipids, pGL3 (Promega, Madison, WI, USA) were complexed with liposomes consisting of DOPE (dioleoylphosphatidylethanolamine; Avanti Polar Lipids, Alabaster, AL, USA) and HyC-Chol (DOPE:HyC-Chol = 2:3 (mol/mol)) to form liposome-DNA complexes. Liposome-DNA complexes were incubated with the cells for 4 h at 37°C, and then the cells were washed and cultured in DMEM for another 24 h at 37°C, followed by a luciferase assay. When cells were treated with nocodazole, which disrupts microtubules, the efficiency of transfection increased dose-dependently and about doubled at 10 m, as shown in Figure 1a. Taxol, which stabilizes microtubules, also enhanced transfection efficiency in a dose-dependent manner (Figure 1b). The concentrations at which these reagents had effects were within the range of their working concentrations to affect microtubules specifically. Therefore, the results suggest that modification of the polymerization states of microtubules changes the efficiency of gene transfection. To examine the possibility that these reagents increased the ability of cells to interact with exogenous liposome-DNA complexes, cells were incubated with the liposome-DNA complexes containing NBD-PE (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl )-1,2-dihexadecanoyl-sn-glycero-3-phospho-

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Section: Figure 4 Effects Of Nocodazole and Taxol On The Distributionmentioning

confidence: 99%

Microtubule involvement in the intracellular dynamics for gene transfection mediated by cationic liposomes

2001

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“…This formulation has severe side effects caused by its Cremophor EL and the organic solvent [183,184]. Consequently, several attempts have been made to increase the poor paclitaxel solubility (0.3 mg/mL) using various formulations or prodrug conjugates [185][186][187][188][189][190][191][192][193]. Kontoyianni, Sideratou and coworkers [194] successfully functionalized commercially available hyperbranched aliphatic polyester Boltorn H40 [63,195,196] with PEG chains to afford a novel water-soluble BH40-PEG polymer exhibiting unimolecular micellar properties appropriate for application as a drug delivery system [194].…”

Section: Methodsmentioning

confidence: 99%

Polyester Dendrimers: Smart Carriers for Drug Delivery

Twibanire

Grindley

2014

Polymers

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Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

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“…Aqueous nanoparticle dispersion equivalent to 30 mg/kg of FU and pure drug solution of FU in saline were administered to rats by intravenous route in tail vein. Three rats per group were used for the study (Ceruti et al, 2000).…”

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

l-Cysteine conjugated polyl-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissuesin vivo

2014

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Context: Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. Objective: In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. Methods: An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. Results and conclusion: The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

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Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing water-soluble prodrugs of paclitaxel

Cited by 75 publications

References 45 publications

Microtubule involvement in the intracellular dynamics for gene transfection mediated by cationic liposomes

Microtubule involvement in the intracellular dynamics for gene transfection mediated by cationic liposomes

Polyester Dendrimers: Smart Carriers for Drug Delivery

l-Cysteine conjugated polyl-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissuesin vivo

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