HYBRID NANOCARRIER LIBRARY BASED BIOMATERIALS FOR THERAPEUTIC APPLICATIONS.

Tumor targeting plays a pivot role in anticancer therapy. Tumor targeting can be carried out by conjugating specific targeting agents on the surface of nanoparticles or modifying their shape and size. To improve the selective targeting and accumulate therapeutic agents inside the tumor tissues, we designed new Discoidal Nanoparticles (DNs) having a non-spherical shape that better interact and cross through the fenestrated endothelium of tumor tissue compared to spherical nanoparticles. These nanoparticles are lipid based and are made up from the same lipids used to make liposomes and are obtained by changing the original spherical shape of liposomes in discoidal and decreasing liposomal native average sizes. Copolymers are basically used to modify spherical shape of liposomes and finally obtain discoidal form. SMAnh is a copolymer synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) between Styrene and Maleic Anhydride and can form nanodisks. Molecular ratio between styrene and maleic anhydride, pH and temperature of microenvironment reaction can however affect the synthesis of nanodiscks [1]. In this work we studied the use of SMAnh as copolymers capable to synthesis DNs starting from spherical liposomes at different molar ratio of copolymer, pH and temperature. MATERIALS AND METHODS Different liposomes were synthesized using thin layer evaporation method, freeze and thaw and extrusion. Liposomes were physicochemical characterized by using Dinamic Light Scattering (DLS) and UV-Vis spectrophotometer. The best selected formulations was DMPC liposomes that was used for further experiments. The DNs are synthesized by incubating the resulting liposomes with SMAnh (Styrene-Anhydride maleic molecular ratio 2:1) in Hepes 10 mM at pH = 7.4 and pH = 6.4. The resulting DNs are further physiochemically characterized by DLS and UV-Vis spectrophotometer. RESULT AND DISCUSSION SMAnh 2:1 molar ratio cannot make only DN at pH = 7.4. UV-Vis absorption of DN increased over time. This effect is directly related to the turbidity of nanoparticles. UV-Vis analysis agreed DLS data that show the presence of three different particle sizes at 5000 nm (80%), 200 nm (13%) and 13 nm (7%). Large particles depend on the presence of free SMAnh making aggregates in incubation medium. Narrow size distributed DN was obtained at pH = 6.4 using SMAnh 2:1 (molar ratio). DLS data shows two different peaks: 200 nm (10%) that represents bare liposomes and 13 nm (60%) that represents DN (Figure 1).