Effects of silymarin-loaded amphiphilic chitosan polymeric micelles on the renal toxicity and anticancer activity of cisplatin.
Pharm Dev Technol
; 24(8): 927-934, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-30526167
ABSTRACT
This research aimed to evaluate the effects of silymarin (SM)-loaded polymeric micelles (PMs) on the renal toxicity and anticancer activity of cisplatin. Amphiphilic chitosan derivatives were employed to develop SM-loaded PMs. The permeation across an intestinal membrane, cytotoxicity, and renal toxicity of cisplatin during the treatment were evaluated. The SM-loaded PMs had small particle sizes (326-336 nm), negative surface charge, high entrapment efficiency (47-70%), and demonstrated pH-sensitive release. Rapid drug release was obtained at pH 7.4 (81-87% in 4 h). The SM-loaded PMs exhibited higher flux than free SM. Moreover, the pretreatment of SM (50-100 µg/mL)-loaded PMs increased the killing efficacy of cisplatin on the cancer cells. The renoprotective effect was witnessed (p < 0.05) on the cells pretreated with SM-loaded benzyl-functionalized succinyl chitosan (BSC) PMs compared with those treated with only cisplatin, which the % cell viability increased from 29% to 82% and 96% for the PMs with SM concentration of 50 and 100 µg/mL, respectively. Moreover, the reduction in cell apoptosis and necrosis induced by cisplatin has been observed. In conclusion, SM-loaded BSC PMs could improve the bioavailability of SM, enhance the therapeutic effect, and protect renal damage during the treatment with cisplatin.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polímeros
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Silimarina
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Cisplatino
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Quitosana
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Rim
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article