Permeation enhancers loaded bilosomes for improved intestinal absorption and cytotoxic activity of doxorubicin

The clinical utility of doxorubicin is compromised due to dose related toxic side effects and limited oral bioavailability with no oral formulation being marketed. Enhancement of intestinal absorption and magnifica-tion of cytotoxicity can overcome these limitations. Accordingly, the objective was to probe penetration en-hancers, bilosomes and their combinations for enhanced intestinal absorption and improved cytotoxicity of doxorubicin. Piperine and dipyridamole were tested as enhancers alone or encapsulated in bilosomes comprising Span60, cholesterol and bile salts. Bilosomes were nanosized spherical vesicles with negative zeta potential and were able to entrap doxorubicin with efficiency ranging from 45.3 % to 53 %. Intestinal absorption studies utilized in-situ rabbit intestinal perfusion which revealed site dependent doxorubicin absorption correlating with regional distribution of efflux transporters. Co-perfusion with the enhancer increased intestinal absorption with further augmentation after bilosomal encapsulation. The latter increased the % fraction absorbed by 4.5-6 and 1.8-2.5-fold from jejuno-ileum and colon, respectively, depending on bilosomes composition. Additionally, doxorubicin cytotoxicity against breast cancer cells (MCF-7) was significantly improved after bilosomal encap-sulation and the recorded doxorubicin IC50 value was reduced from 13.3 mu M to 0.1 mu M for the best formulation. The study introduced bilosomes encapsulating absorption enhancers as promising carriers for enhanced cyto-toxicity and oral absorption of doxorubicin.

Automated summary

This study investigated the use of bilosomes encapsulating absorption enhancers as carriers for enhancing the oral absorption and cytotoxicity of doxorubicin. The bilosomes were found to significantly improve the intestinal absorption and cytotoxicity of doxorubicin against breast cancer cells.