Studies on the intracerebral injection of vincristine free and entrapped within liposomes in the rat

Oliver, Andrew; Firth, Gary; McKeran, R O

doi:10.1016/0022-510x(85)90047-4

Cited by 15 publications

(11 citation statements)

References 4 publications

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“…Small unilamellar vesicles having an interstitial half-life of 14 h may be used as a faster component of a composed therapy system. [3,8,11,13]; dies ist neben anderen pharmakologischen Faktoren (wie Dosierung und Chemosensitivität der Tumoren) ein Grund, weshalb entspre chende intratumorale bzw. postoperativ intrakavitäre Zytostatikaapplikationen [4,14] …”

Section: Summary and Abstractunclassified

CT-Kinetik intratumoraler Liposomendepots

et al. 1988

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An einem experimentellen Rattentumormodell wurden computertomographisch intratumorale Depots von Metrizamid-beladenen Liposomen untersucht. Das Untersuchungsmodell hat sich als einfache, klinischen Bedürfnissen angepaßte Methode zur Bestimmung der In-vivo-Kinetik dieser interstitiellen Kontrastmitteldepots erwiesen. Gegenüber freiem, intratumoral appliziertem Metrizamid, das als Modellsubstanz für ein wasserlöslíches Chemotherapeutikum angesehen werden kann, zeigt liposomal gebundenes Metrizamid eine deutlich verzögerte Abnahme der Röntgenabsorption. Dieser Retard-Effekt war bei großen, multilamellaren Vesikeln wesentlich ausgeprägter als bei kleinen, unilamellaren Vesikeln. Ohne daß eine Diffusion der Liposomen nachzuweisen war, sanken die Beträge der Hounsfield-Einheiten bei beiden Typen verlangsamt ab; bei multilamellaren Liposomen signifikant im Sinne einer Kinetik nullter Ordnung mit einer Halbwertszeit von ca. 300 h. Eine initial mit einem Anstieg der Houns-field-Werte einhergehende Abweichung von dieser Kinetik wird auf einen Konzentrationseffekt innerhalb der Liposomendepots infolge eines Abstroms des wässerigen Anteils der Liposomendispersíon zurückgeführt. Aufgrund des ausgeprägten Retard-Effektes der großen multilamellaren Liposomen, der eine 140fache Verlängerung der loka-len Verweildauer des Metrizamids bewirkt und aufgrund ihrer Freisetzungskinetik empfiehlt sich diese Liposomenart als Carriersystem für eine lokale interstitielle Chemotherapie von Hirntumoren. Kleine, unilamellare Liposomen, die eine interstitielle Halbwertszeit von 14 h aufweisen, könnten als schnellere Komponente eines komplexeren Therapiesystems angewandt werden.

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Section: Summary and Abstractunclassified

CT-Kinetik intratumoraler Liposomendepots

et al. 1988

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“…The same authors tested rat brain after injection of vincristine, free and entrapped within liposomes [46]. Only one animal, that which had received the highest dose of free vincristine injection, showed a marked behavioral change.…”

Section: Experimental Datamentioning

confidence: 99%

“…In experimental animals, however, dose-related toxicity was observed after intracerebral injection of methotrexate [61], CCNU [37], bleomycin [38,45] and vincristine [46]. Histological changes in the normal brain of experimental animals ranged from only mechanical trauma by needling after doxorubicin [62] and bleomycin [39,45], to variable degree of necrosis after ACNU [32] and vincristine [46].…”

Section: Toxicitymentioning

confidence: 99%

“…Histological changes in the normal brain of experimental animals ranged from only mechanical trauma by needling after doxorubicin [62] and bleomycin [39,45], to variable degree of necrosis after ACNU [32] and vincristine [46]. Although Merker et al reported an uniformly fatal necrotizing angiopathy after intrathecal administration of doxorubicin [63], the intracavitary or intracerebral injection of this drug in both humans and rats did not cause devastating results [24,25,62].…”

Section: Toxicitymentioning

confidence: 99%

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Interstitial chemotherapy for brain tumors: review

Tomita

1991

J Neuro-Oncol

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An extensive effort to search for curative chemotherapeutic approaches has found no 'breakthrough' in management of patients with malignant brain tumors. Despite the trials with new agents or protocols of multiple agents, systemic chemotherapy has failed to provide reliable clinical response. Interstitial chemotherapy has been practiced for malignant brain tumors with administering chemotherapeutic compounds directly into the tumor which provide increased and prolonged drug concentration in the tumor, reduction of systemic toxicity and bypassing the blood-brain barrier. These theoretical advantages encourage further pursuing interstitial chemotherapy for patients with malignant brain tumors who would otherwise be always fatal. In this review, the literature has been reviewed to identify methods, toxicity, and efficacy of interstitial chemotherapy. Clinical and experimental data indicate limited toxicity and promising efficacy. Various methods to administer the agents were utilized; intraoperative topical application, local injections through catheters or implantable controlled drug delivery system. Selection of ideal chemotherapeutic agents and development of drug delivery system need further investigations.

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“…6) (Figs. 9-11 (24,36) and, unlike other lipophilic Yi nca alkaloids (1), exert no overt central nervous system toxicity unless they are accidentally delivered to the brain (11,13,42 (19,20,32,33,37).…”

Section: Introductionmentioning

confidence: 99%

Peripheral Neuropathy Induced by Intravenous Administration of Vincristine Sulfate in the Rabbit.

et al. 1995

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The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic agent vincristine sulfate (VCR) has hampered the correlation between experimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR total dosage similar to that used in humans, a peripheral polyneuropathy characterized by electrophysiological changes that overlap those observed in the clinical setting. The present study was aimed at investigating the ultrastructural features of 3 different nerves (sural, peroneal, and medial gastrocnemius) in rabbits treated with 3 VCR doses that fall within the range (0.2-0.3 mg/kg iv) known to be efficacious chemotherapeutically and active neurotoxicologically. Regardless of the dose and the nerve under examination, histopathologic alterations appeared in the form of an overall loss of myelinated fibers, accompanied by successful attempts of regeneration and remyelination. Fibers undergoing Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a consequence of ingrowing Schwann cell processes from the adaxonal surface. These ingrowths tended to isolate axoplasmic areas, retaining a fairly normal structure from other areas already crowded with altered organelles and cytoskeletal elements. In any event, neurofibrillary accumulations were rarely seen. These patterns are discussed with reference to those reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripheral neuropathy.

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Studies on the intracerebral injection of vincristine free and entrapped within liposomes in the rat

Cited by 15 publications

References 4 publications

CT-Kinetik intratumoraler Liposomendepots

CT-Kinetik intratumoraler Liposomendepots

Interstitial chemotherapy for brain tumors: review

Peripheral Neuropathy Induced by Intravenous Administration of Vincristine Sulfate in the Rabbit.

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