Evaluation of the Antitumour Activity of Liposomal Formulations of Etoposide Against Choriocarcinoma Xenografts in Balb/c nu/nu Mice

Tyagi, Pradeep; Sengupta, Shiladitya; Velpandian, Thirumurthy; Gupta, Yogendra Kumar; Kochupillai, V.; Gupta, Sudheer

doi:10.1211/146080899128734190

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…In preliminary experiments, we had observed an enhancement in the efficacy of etoposide against choriocarcinoma following liposome-mediated delivery [18]. Similar observations have also been noted with other antineoplastic drugs such as vincristine [25], doxorubicin [26] and taxol [27].…”

Section: Discussionsupporting

confidence: 70%

“…The non-encapsulated free drug was then separated from the liposomal component by centrifugation at 10,000 g for 15 min under which conditions the liposomes remain suspended and etoposide precipitates are sedimented, then passing through a Sephadex G 25 column (Pharmacia) with PBS as eluant. The liposomes were analysed for percentage encapsulation of etoposide using spectrophotometry [18] using a Beckman DU600 spectrophotometer. Liposomes were sized using electron microscopy [19].…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…At this juncture the mice were treated according to the treatment schedule shown in table 1 and the first day of treatment was considered as day 0. The total concentration of pure drug in 1 ml of liposomal preparation was calculated by lysis of an aliquot of liposome suspension followed by spectrophotometry [18] and appropriate dilutions were made in PBS. The drug and vehicle were slowly injected into the tail vein with a 27-gauge needle and the total volume of administration never exceeded 100 Ìl per dose.…”

Section: Treatment Schedule and Assessment Parametersmentioning

confidence: 99%

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Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor

Sengupta¹,

Tyagi²,

Chandra³

et al. 2001

Pharmacology

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Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm³ in volume. Liposomal etoposide (10 mg/m²/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.

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Section: Discussionsupporting

confidence: 70%

Section: Preparation Of Liposomesmentioning

confidence: 99%

Section: Treatment Schedule and Assessment Parametersmentioning

confidence: 99%

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Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor

Sengupta¹,

Tyagi²,

Chandra³

et al. 2001

Pharmacology

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“…The higher lipophilicity of ETP offers better intercalation in lipid-based liposomal formulations (18,19). Liposomes accumulate in the tumors in a gradual passive fashion due to increased "leakiness" of the tumor vasculature (20).…”

Section: Introductionmentioning

confidence: 99%

Tuftsin Augments Antitumor Efficacy of Liposomized Etoposide against Fibrosarcoma in Swiss Albino Mice

Khan

Dwivedi

et al. 2007

Mol Med

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Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma.

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“…O veículo também tem influência na função do endotélio e músculos, causando vasodilatação, dificuldade respiratória, letargia e hipotensão (WEISS et al, 1990;ROWINSKY et al, 1990;PAZDUR et al, 1993). LUNDBERG, 1994;KAN et al, 1999;JURCIC;SCHEINBERG;HOUGHTON, 1996;TYAGI et al, 1999;SENGUPTA et al, 2000; BELLOT; POUNA; ROBERT, 2001). et al, 1981).…”

Section: Paclitaxelunclassified

Paclitaxel e metotrexato associados a uma nanoemulsão lipídica no tratamento da aterosclerose em coelhos

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Evaluation of the Antitumour Activity of Liposomal Formulations of Etoposide Against Choriocarcinoma Xenografts in Balb/c nu/nu Mice

Cited by 8 publications

References 13 publications

Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor

Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor

Tuftsin Augments Antitumor Efficacy of Liposomized Etoposide against Fibrosarcoma in Swiss Albino Mice

Paclitaxel e metotrexato associados a uma nanoemulsão lipídica no tratamento da aterosclerose em coelhos

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