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 作者： João Hélio Venâncio, Lígia Marquez Andrade, Najla Locali Santos Esteves, Lara Barroso Brito, Marize Campos Valadares, Gisele Augusto Rodrigues Oliveira, Eliana Martins Lima, Ricardo Neves Marreto, Tais Gratieri, Stephânia Fleury Taveira

 

 

摘要：

Objectives

 

This work aimed to evaluate semisolid formulations containing topotecan (TPT) loaded nanostructured lipid carriers (NLC) for topical treatment of skin cancers, as TPT is effective against a variety of tumours. A formulation which increases TPT skin permeation would be extremely desirable.

Methods

 

TPT-NLC were prepared and incorporated in hydrogels with hydroxyethyl cellulose and chitosan (TPT-NLC-HEC and TPT-NLC-Ch, respectively). Control formulations were obtained by dispersing TPT in HEC and Ch hydrogels (TPT-HEC and TPT-Ch).

Key findings

 

TPT-NLC-HEC and TPT-NLC-Ch showed to maintain the drug and nanoparticle dispersions stable for up to 30 days. When nanoparticles were incorporated into gels, TPT release was significantly decreased (P < 0.05). Still, TPT-NLC-HEC increased 2.37 times permeation compared with TPT-HEC (11.9 and 5.0 μg/cm2, respectively). Cell culture experiments with B16F10 melanoma demonstrated that nanoencapsulation significantly increased TPT cytotoxicity (P < 0.05). TPT-NLC was more toxic than free TPT, with IC50 value of 5.74 μg/ml, whereas free TPT had an IC50 > 20 μg/ml. As skin permeated values of TPT from developed formulation (TPT-NLC) were superior to melanoma IC50, it can be extrapolated that chemotherapeutic permeated amounts may be sufficient for a therapeutic effect.

Conclusions

 

TPT-NLC-HEC may be a valuable tool for the topical treatment of skin cancers.