5-Fluorouracil plasma levels and biodegradation of subcutaneously injected drug-loaded microspheres prepared by spray-drying poly(d,l-lactide) and poly(d,l-lactide-co-glycolide) polymers

Sastre, R.; Olmo, Rosa; Teijón, César; Muñiz, E; Teijón, José M.; Blanco, Marcos

doi:10.1016/j.ijpharm.2007.02.001

Cited by 56 publications

(37 citation statements)

References 45 publications

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“…Analysis of the results of cytotoxicity studies followed by AO/EB assay and FACS depict that PLGA 50-50 nanoparticles showed better potency than 90-10 nanoparticles in both the cell lines, indicating the variation in cytotoxicity with the lactide/glycolide combination of PLGA used. Although the potential of 5-FU-loaded PLGA microspheres has already been reported, 38,[42][43][44] limitations associated with their size restrict their efficacy in cancer therapy. Since data from the literature show that continuous infusion of low-doses is an excellent regimen for inducing cell death more effectively than a single high-dose exposure, 45 it supports the idea that nanoparticle-based sustained-release formulations could be very promising in improving the efficacy of therapeutic agent.…”

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confidence: 99%

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

K¹,

Jagadeeshan²,

Nair³

et al. 2011

IJN

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Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.

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mentioning

confidence: 99%

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

K¹,

Jagadeeshan²,

Nair³

et al. 2011

IJN

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“…This fact can be considered in accordance with the normal body reaction to a biocompatible material, which consists in walling it off in an avascular, collagenous bag. This event was also observed after the injection of unloaded and 5-FU-loaded PLA and PLGA microspheres [38].…”

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confidence: 64%

“…Furthermore, 35 and 50 mg/Kg b.w. have been subcutaneously administered in rats by polyester microspheres [38]. Hence, the dose utilized in our experiment was in accordance with above mentioned doses.…”

Section: In Vivo Studies: Biocompatibility and Pharmacokineticmentioning

confidence: 99%

In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System

et al. 2011

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Folate-targeted poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] nanohydrogel (F-SubMG) was loaded with 5-fluorouracil (5-FU) to obtain low (16.3 ± 1.9 μg 5-FU/mg F-SubMG) and high (46.8 ± 3.8 μg 5-FU/mg F-SubMG) load 5-FU-loaded F-SubMGs. The complete in vitro drug release took place in 8 h. The cytotoxicity of unloaded F-SubMGs in MCF7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 μM 5-FU by 5-FU-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was higher in HeLa cells because they are folate receptor positive. After subcutaneous administration (28 mg 5-FU/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin. Histological studies indicated that the OPEN ACCESSPolymers 2011, 3 1108 F-SubMGs were surrounded by connective tissue, without any signs of rejections, even 60 days after injection. Pharmacokinetic study showed an increase in MRT (mean residence time) of 5-FU when the drug was administered by drug-loaded F-SubMGs.

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“…They reported that uniform genipin-gelatin microcapsules would provide many potential usages for pharmaceutical applications. Sastre et al (2007) prepared microspheres of 5-FUloaded poly(D, L-lactide), poly(D, L-lactide-co-glycolide) 75:25 and poly(D, L-lactide-co-glycolide) 50:50 by the spraydrying technique and subcutaneously injected in the back of Wistar rats in order to evaluate the 5-FU release and biodegradation characteristics. Huang et al (2010) prepared chitosan/chondroitin sulfate complex microcapsules to encapsulate the 5-FU by emulsion-chemical crosslinking method.…”

Section: Introductionmentioning

confidence: 99%

Preparation of ferric ion crosslinked acrylamide grafted poly (vinyl alcohol)/sodium alginate microspheres and application in controlled release of anticancer drug 5-fluorouracil

Şanlı

Olukman

2013

Drug Delivery

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Ionically crosslinked microspheres of acrylamide (AAm) grafted poly (vinyl alcohol) (PVA)/ sodium alginate (NaAlg) were prepared by crosslinking with FeCl 3 and 5-fluorouracil (5-FU), which is an anticancer drug and was successfully encapsulated into the microspheres. The graft copolymer (PVA-g-PAAm) was characterized by using Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The prepared microspheres were characterized by FTIR and scanning electron microscopy (SEM). Microspheres were also characterized by particle diameter, equilibrium swelling values and release profiles. The release studies were carried out at three pH values 1.2, 6.8 and 7.4, respectively, each for 2 h. The effects of preparation conditions as PVA-g-PAAm/NaAlg ratio, drug/polymer ratio, crosslinker concentration and exposure time to FeCl 3 on the release of 5-FU were investigated for 6 h at 37 C. The highest 5-FU release was found to be as 99.57% (w/w) at the end of 6 h for PVA-g-PAAm/NaAlg ratio of 1:4 (w/w), drug/ polymer ratio of 1:8 (w/w), crosslinker concentration of 0.05 M and exposure time of 10 min. The release results were also supported by the swelling measurements of the microspheres. Release kinetics was described by Fickian and non-Fickian approaches.

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5-Fluorouracil plasma levels and biodegradation of subcutaneously injected drug-loaded microspheres prepared by spray-drying poly(d,l-lactide) and poly(d,l-lactide-co-glycolide) polymers

Cited by 56 publications

References 45 publications

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System

Preparation of ferric ion crosslinked acrylamide grafted poly (vinyl alcohol)/sodium alginate microspheres and application in controlled release of anticancer drug 5-fluorouracil

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