Therapeutic efficacy study of novel 5-FU-loaded PMM 2.1.2-based microspheres on C6 glioma

Fournier, E; Passirani, Catherine; Vonarbourg, Arnaud; Lemaire, Laurent; Colin, Nathalie; Sagodira, Serge; Menei, Philippe; Benoit, Jean‐Pierre

doi:10.1016/j.ijpharm.2003.08.014

Cited by 19 publications

(8 citation statements)

References 8 publications

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“…The results were given in Figure 6, which clearly indicated that increasing exposure time to FeCl 3 decreased the cumulative release of 5-FU. Similar results were given in the literature [4,11,12,14]. Although the maximum 5-FU release from the Fe-Alg beads was obtained with the exposure time of 5 min., since these beads did not stand to pH value of 7.4.…”

Section: Effect Of Exposure Time To Crosslinker On the 5-fu Releasesupporting

confidence: 90%

“…Since its active form inhibits DNA synthesis by inhibiting the normal production of thymidine. It has a relatively high response in colon, rectal, breast, gastrointestinal tract pancreas, head, ovarion cancers [1][2][3][4]. The common method of administration of 5-FU is in the form of injections into vein [1,5,6] (intravenous) or as an infusion.…”

Section: Introductionmentioning

confidence: 99%

“…There are many studies in the literature for encapsulation of 5-FU in polymeric materials. In those studies [1,2,4,[6][7][8][9][10][11][12][13]. Generally natural polymers were preffered to syn-thetic polymers for the encapsulation because of their free aviability, nontoxicity and biodegrability characteristics.…”

Section: Introductionmentioning

confidence: 99%

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Release of Anticancer Drug 5-Fluorouracil from Different Ionically Crosslinked Alginate Beads

Olukman¹,

Şanlı²,

Solak³

2012

JBNB

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In this research; the release of 5-Fluorouracil (5-FU) from different ionically crosslinked alginate (Alg) beads was investigated by using Fe3+, Al3+, Zn2+, and Ca2+, ions as crosslinking agent. The prepared beads were characterized by Fourier Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry (DSC) and Scanning Electron Micros-copy (SEM). The drug release studies were carried out at three pH values 1.2, 6.8 and 7.4 respectively each for two hours. The effects of the preparation conditions as crosslinker type, drug/polymer (w/w) ratio, crosslinker concentration and time of exposure to crosslinker on the release of 5-FU were investigated for 6 hours at 37℃. It was observed that 5-FU release from the beads followed the order of Fe > Zn > Al > Ca-Alg and increased with increasing drug/polymer ratio. At the end of 6 hours, the highest 5-FU release was found to be 90% (w/w) for Fe-Alg beads at the drug/polymer ratio of 1/8 (w/w), crosslinker concentration of 0.05 M, exposure time of 10 minutes respectively. The swelling measurements of the beads supported the release results. Release kinetics was described by Fickian and non-Fickian approaches

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Section: Effect Of Exposure Time To Crosslinker On the 5-fu Releasesupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Release of Anticancer Drug 5-Fluorouracil from Different Ionically Crosslinked Alginate Beads

Olukman¹,

Şanlı²,

Solak³

2012

JBNB

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“…Cardiac, hematological, neural, and dermatological toxic side effects are also severe via intravenous administration. However, oral administration using controlled release formulations significantly reduced the side effects [31, 32]. Many polymer materials have been reported for the encapsulation and in vitro release of 5-FU [33].…”

Section: Introductionmentioning

confidence: 99%

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil

et al. 2017

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There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.

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“…To estimate clinically relevant concentrations, we used the following information: routinely used continuous intravenous infusions of 5-FU can result in steady-state plasma and cerebrospinal fluid (CSF) concentrations in the range 0.3–71.0 μM, and continuous pump infusions result in 3- to 25-fold higher levels of exposure [ 80 ]. High-dose (bolus) injections of 5-FU can even expose brain tissue to peak concentrations in the millimolar range [ 80 , 81 ], with tri-exponential elimination half-time values of 2, 12 and 124 minutes [ 82 ], and CSF elimination half-times can be greatly extended after localized application to brain tissue using slowly biodegradable polymer microspheres [ 83 , 84 ].…”

Section: Resultsmentioning

confidence: 99%

Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

Han

Yang

Dietrich

et al. 2008

J Biol

258

168

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BackgroundCancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem.ResultsWe found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent) were toxic for both central nervous system (CNS) progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment.ConclusionsOur studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

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Therapeutic efficacy study of novel 5-FU-loaded PMM 2.1.2-based microspheres on C6 glioma

Cited by 19 publications

References 8 publications

Release of Anticancer Drug 5-Fluorouracil from Different Ionically Crosslinked Alginate Beads

Release of Anticancer Drug 5-Fluorouracil from Different Ionically Crosslinked Alginate Beads

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil

Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

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