INFLUENCE OF SURFACE MODIFICATIONS OF DENDRITIC POLYMERS IN THEIR INTERACTION WITH ALBUMIN.

L. FERNÁNDEZ, V ANGELLI, M. CALDERÓN, M. MARTINELLI, M. STRUMIA, M. SANTO, J.J. SILBER

Los Cocos- Córdoba

Simposio; III Argentine-Chilean Polymer Symposium; 2005

Comité Organizador

Dendrimers are highly branched three-dimensional polymers, with all bonds originating from a central core. Compared with conventional linear polymers, dendrimers have further precisely controlled structures, with a generally globular construct, a single molecular weight and a large number of controllable peripheral terminal groups. (Liu and Fréchet, 1999). Dendrimers have found a number of biomedical applications. (Estefan and Tomalia, 2001). Functional groups presented on the surface have been utilized for the conjugation of drugs. (Chen and Cooper, 2000). In addition, a dendrimer interior has been show to be capable of encapsulating  various molecules. (Morgan et al, 2003). Since dendrimers have a symmetrical spherical topology the molecules described in this communication termed dendrons are asymmetrical. They have multiple aromatic head group couple to a lipophilic tail and different terminal groups. These dendrons will be utilized in the convergent synthesis of water-soluble dendrons to be evaluated as potential drug carriers. In view of the use of these macromolecules for drug delivery, it is necessary to know their biological properties such as toxicity and biocompatibility. The circulation system seems to be the most convenient way of drug administration because an active compound within a relatively short time is able to reach distant tissues, which are unavailable directly. However, blood constituents can be the first and unwanted targets of drug action. Binding to plasma proteins and blood vessel walls may lead serious problems of toxicity or at least dramatically lower the amount of drug available for therapy.(Domanski el all, 2004) In the present work we investigated the interaction between tris-dendrons and human serum albumin (HAS). Serum albumin is the most abundant soluble protein constituent of circulatory system, have many physiological functions as contribute to colloid osmotic blood pressure and be chiefly responsible for the maintenance of blood pH. These molecules are the principal carriers of fatty acids and have high affinity for negatively charged hydrophobic molecules.(Gao et all, 2004) The impact of tris-dendrons in HAS was evaluated by the measurement of the intrinsic fluorescence intensity of protein L-tryptophan residues before and after addition of dendrons. This protein had a strong fluorescence emission band at 342 nm by fixing the excitation wavelength at 285 nm. The fluorescence intensity of HAS decreased regularly with increase of Dendron 1 concentration. The reduction in the fluorescence intensity of tryptophan residue was less pronounced for Dendron 2. The impact of dendron 3 in HAS could not be evaluated due to the low solubility of dendron 3 in water. In conclusion, our experiment showed that there are interactions between tris-dendrons and HAS. It is probable that the interactions are electrostatic in nature and cause HAS conformational changes although more detailed analysis is needed to resolve this matter. HAS fluorescence was strongly quenched by cyano terminal dendrons, but was only poorly quenched by ester terminal dendrons, as it is reflected from the value of the Ksv constant These results indicated than the extension of the impact depends strongly on their surface groups.