Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with markedin vivoantitumor activity
Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p < 0.001) without causing any explicit toxicity. The 6.5 mg/kg and 3 mg/kg oral PTXL nanoemulsion dose did not cause any notable alteration in haematological, biochemical/structural characteristics during 28-day sub-chronic toxicity studies in the experimental mice. Whereas, the toxicity of 12.8 mg/kg body weight dose showed decrease in RBC, haemoglobin and neutrophil counts. In contrast, marketed PTXL (Taxol®) was found to be comparatively more toxic to the experimental animals. Taxol® treatment resulted glomerulonephritis in histopathological examination, which could be correlated with increased level of creatinine and associated nephrotoxicity. This investigations conclude that the developed oral nanoemulsion presents a viable therapeutics bio-system to step towards clinical application as well as substitute CrEL based PTXL formulations.