Human Serum Albumin Nanoparticles as a Carrier for On-demand Sorafenib Delivery

Background: Drug delivery systems based on Human Serum Albumin (HSA) have been widely investigated due to their capability to interact with several molecules together with their nontoxicity, non-immunogenicity and biocompatibility. Sorafenib (SOR) is a kinase inhibitor used as the first-line treatment in hepatic cancer. However, because of its several intrinsic drawbacks (low solubility and bioavailability), there is a growing need for discovering new carriers able to overcome the current limitations. Objectives: To study HSA particles loaded with SOR as a thermal responsive drug delivery system. Methods: A detailed spectroscopy analysis of the HSA and SOR interaction in solution was carried out in order to characterize the temperature dependence of the complex. Based on this study, the synthesis of HSA particles loaded with SOR was optimized. Particles were characterized by Dynamic Light Scattering, Atomic Force Microscopy and by spectrofluorometer. Encapsulation efficiency and in vitro drug release were quantified by RP-HPLC. Results: HSA particles were monodispersed in size (approximate to 200 nm); encapsulation efficiency ranged from 25% to 58%. Drug release studies that were performed at 37 degrees C and 50 degrees C showed that HS5 particles achieved a drug release of 0.430 mu M in 72 hours at 50 degrees C in PBS buffer, accomplishing a 4.6-fold overall SOR release enhancement following a temperature increase from 37 degrees C to 50 degrees C. Conclusion: The system herein presented has the potential to exert a therapeutic action (in the nM range) triggering a sustained temperature-controllable release of relevant drugs.