Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

Leite, Elaine Amaral; Giuberti, Cristiane dos Santos; Wainstein, Alberto Julius Alves; Wainstein, Ana Paula D.L.; Coelho, Luiz G V; Lana, Ângela Maria Quintão; Savassi-Rocha, Paulo Roberto; Oliveira, Mônica Cristina

doi:10.1016/j.lfs.2009.02.002

Cited by 45 publications

(27 citation statements)

References 16 publications

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“…In the biodistribution assays, two-way analysis of variance (ANOVA) was used to compare differences between the groups. To analyze the variation in body weight, the value before treatment was used as the covariate, 24 and one-way ANOVA, followed by Bonferroni's post-test, was used to compare differences between the groups. To analyze biochemical parameters, the computed normalized absorbance ratios were used, by correcting the mean optical density value for each sample from NQ, NQC, NQC-AmpB, and free AmpB groups, and dividing it by the mean optical density value from the control group.…”

Section: Discussionmentioning

confidence: 99%

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Ribeiro¹,

Franca²,

Fuscaldi³

et al. 2014

IJN

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Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis . An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Ribeiro¹,

Franca²,

Fuscaldi³

et al. 2014

IJN

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“…Notably, investigations have shown that about 20% of acute renal failure cases among hospitalized patients are due to platinum-based chemotherapy [4,19,22,27]. Several authors agree that renal damage due to cisplatin is irreversible.…”

Section: Discussionmentioning

confidence: 99%

Cystatin C – A Fast and Reliable Biomarker for Glomerular Filtration Rate in Head and Neck Cancer Patients

et al. 2011

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“…The encapsulation of CDDP in liposomes did not affect the size or the zeta potential of the liposomes, as we previously reported. 7,8 The encapsulation percentage of CDDP into liposomes proved to be similar in both SpHL-CDDP and NSpHL-CDDP. All formulations offered an appropriate size and homogeneity for IV administration.…”

Section: Discussionmentioning

confidence: 89%

“…6 The present study's research group has developed longcirculating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) which previously showed both two-and three-fold higher values of median lethal doses than those obtained for free CDDP after their intravenous (IV) and intraperitoneal administration in healthy mice, respectively. 7,8 At the same time, hematological investigations revealed no alteration in red and white blood cell counts upon SpHL-CDDP administration in mice. In addition, SpHL-CDDP treatment caused no pronounced alterations in the blood urea and creatinine levels, nor did it induce morphological alterations in the kidneys of the mice.…”

Section: Introductionmentioning

confidence: 87%

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

Leite¹,

Souza²,

Carvalho-Junior³

et al. 2012

IJN

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Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non-pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL-CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.

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Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

Abstract: These findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.

Cited by 45 publications

References 16 publications

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Cystatin C – A Fast and Reliable Biomarker for Glomerular Filtration Rate in Head and Neck Cancer Patients

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

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