| Abstrakt: |
Sorafenib, a multikinase inhibitor, is used for the treatment of advanced stages of hepatic and renal carcinoma patients. However, sorafenib’s low solubility, low bioavailability, unfavorable pharmacokinetic properties, and undesirable side effects are barriers that restrict its utility. This study aims to overcome these problems by encapsulating sorafenib in a novel camel milk casein nanoparticles. Calcium chloride–linked casein nanoparticles were prepared, lyophilized, and characterized for size distribution, zeta potential, and polydispersity index by using a zeta sizer. Drug encapsulation efficiency and drug loading efficiency of these nanoparticles were also determined by UV spectroscopy. Further, in vivo pharmacokinetic and biodistribution studies were conducted in healthy Swiss albino mice. Bioanalytical method was developed by HPLC for quantitative evaluation of the drug in mice plasma, liver, lungs, kidney, heart, and spleen. Multiple pharmacokinetic parameters like T1/2, AUC, clearance, etc. were analyzed through Phoenix Winolin software. Our pharmacokinetic study showed that sorafenib encapsulation within casein nanoparticles (SFN-CasNPs) significantly increased its bioavailability, as exhibited by an enhanced Cmax(3.8-fold) and AUC (1.42-fold). Also, the half-life (t1/2))of the encapsulated drug increased by 2 h as compared to free drug. Furthermore, biodistribution study showed an increased accumulation of SFN-CasNPs in the liver and kidney as compared to all other tissues, whereas the free drug showed its maximum accumulation in the heart indicating cardiotoxicity. This accumulation of sorafenib was significantly reduced when it was encapsulated within the camel milk casein nanoparticle. This study has highlighted the significance of using camel milk casein nanoparticles for drug delivery owing to an enhanced bioavailability of the sorafenib in an encapsulated form. The reduced accumulation of sorafenib in an encapsulated form also indicates a reduced risk of cardiotoxicity. In the future, clinical trials may be performed on hepatocellular caricinoma patients, after enhancing the selectivity of the drug towards the liver. |
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