PROTEIN ALBUMIN NANOPARTICLE: characterization and biotoxicity

SIRI MACARENA; PRIETO JIMENA; TORCHIO GABRIELA; GRASSELLI MARIANO; ALONSO SILVIA DEL V.

Caxambu

Congreso; XXIX Reunion Anual de FeSBE; 2014

FeSBE

Protein nanoparticles are used to carry and deliver drugs to disease tissues. They constitute an alternative to classical protein?ligand complexes and Emodin is a novel drug that displays interesting anticancer activities. A BSA nanoparticle was synthesized by gamma irradiation; this new nanoparticle is of 50-70 nm size, has been characterized and influence of Emodin- nanoparticle?BSA interactions over the protein bioconjugate Emodin?BSA, related to the protein structure was studied. Objective: The aim of this work was to characterize structure-function of this new drug carrier system and stablish its biotoxicity where the unit (BSA molecule) is known for the specific and non specific binding of hydrophobic drugs, in particular with Emodin. Methods: Different assays such as, T.E.M, UV- visible, light scattering, FTIR, fluorescence, drug affinity for the carrier were carried out, as well as biotoxicity tests in a Zebrafish model. Results: Results showed that the nanoparticle shows a more compact structure with FTIR data of main peaks shifted to the blue region. No loss of functionality of the protein nanoparticle was observed. Parallel studies at different pHs with Emodin confirmed the structure adopted by Emodin on binding to the nanoparticle in sites I and II. When the interaction Emodin? BSA nanoparticle was studied by UV-Vis and value of the binding constant by static fluorescence is indicative of a high affinity (70%) and binding in the order of c.a. 104. Regarding biotoxicity assays, mobility, malformation, and heartbeat rhythm were studied. Collected data showed that when alone, both carriers (BSA nanoparticles vs BSA molecular protein) do not present significative differences, whereas, bound to Emodin, the BSAn-Emodin biconjugate did not present serious secondary effects, and the drug toxicity is effects reduced. This was not the same for the BSA-Emodin biconjugate which presented lethal in cardiotoxicity on the animal model studied. Biotoxicity is discussed in depth analyzing actual controversies on nanoparticles toxicity under present regulatory dispositions. Conclusion: The results presented here will help to further understand the nanoparticles?protein?drug interactions and the role that Emodin-BSA nanoparticles may play in biomedical and pharmacological applications.