Nanoemulsion for enhanced absorption and anti-tumor activity of dasatinib

Abstract

Dasatinib showed encouraging activity on triple-negative breast cancer. However, its minute oral bioavailability (about 34 %) is problematic. This minimum bioavailability is related to poor dissolution, low intestinal permeation and pre-systemic metabolism. The aim was to develop and evaluate SEDD for dissolution and permeability enhancement. Cinnamon oil with Tween 80 were utilized as principal composition (F1) with ethanol (F2) or PEG 200 (F3). The developed SEDDS was in the nanoscale after reconstitution. SEDDS hastened dasatinib dissolution with superiority of F2. In-situ rabbit intestinal absorption from aqueous solution verified the incomplete absorption with input from P-gp efflux. This was shown from the length needed for 95 % absorption (L95 %) which was 305.76, 388.38 and 224.85 cm for duodenum, jejuno-ileum and colon, respectively. Delivering dasatinib as nanoemulsion resulting from reconstitution of F2, enhanced intestinal absorption to reduce L95 % to 104.54, 155.84 and 58.91 in the same segments, respectively. The in vivo antitumor activity proved the superiority of nanoemulsion resulting from F1 and F2 compared with aqueous dispersion with F2 being more promising. The research introduced cinnamon oil SEDDS for augmented dasatinib dissolution, intestinal permeation and subsequently in vivo efficacy.