SYNTHESIS AND CHARACTERIZATION OF AMPHIPHILIC OF POLY(EPSILON-CAPROLACTONE)-POLY(ETHYLENEGLYCOL) BLOCK CO-POLYMERS. OPTIMIZATION OF THE SOLUBILITY ANDTHE STABILITY OF RIFAMPICIN BY MEANS OF ENCAPSULATION INTO POLYMERIC MICELLES

MARCELA A. MORETTON; ROMINA J.GLISONI; DIEGO A. CHIAPPETTA; ALEJANDRO SOSNIK

Santa fé, Argentina.

Congreso; 1º Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos. BIOOMAT 2009.; 2009

Tuberculosis (TB) is a highly contagious disease that still causes the death of young people and adults in the whole world. Rifampicin (RIF) is one of the first-line drugs used in tuberculosis treatment. The World Health Organization has expressed the concern regarding the low stability and bioavailability after the oral administration. There is also a need to adjust the dose to the body weight. Causes of major incidence are: (i) RIF hydrolysis in gastric medium to the insoluble and poorly absorbed 3-Formyl rifamycin SV (3-FRSV) and (ii) RIF incompatibility with another drug of the first line: isoniazid. It is because of these limitations that different approaches have been pursued to improve the solubility, stability and bioavailability of RIF. Our research group is interested in the study of the polymeric micelles as tools to improve water solubility, stability and bioavailability of drugs involved in the treatment of diseases with high social and economical impact. Poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers are polymeric micelle-forming amphiphiles that have been entensively studied as drug carriers. Its high biocompatibility has determined the approval of some of them by the FDA for use in pharmaceutical products. Nevertheless, preliminary assays of RIF encapsulation with different derivatives of these biomaterials indicated their low encapsulation capacity (only 2-fold increase), probably due to the high molecular weight of the drug (823 Da) and its bulky structure. In this framework, we have designed and synthesized novel amphiphilic block copolymers made of poly-(epsilon-caprolactone)-poly (ethylene glycol) (PCL-PEG). The aggregation properties and solubilization ability are currently being investigated. For the synthesis, ring opening polymerization reactions were conducted by microwave-assisted polymer synthesis (MAPS). This technology is extensively used in organic synthesis due to remarkable advantages such the reduction of reaction times and the minimal production of secondary products. Also, due to the homogeneity of the radiation, the reactions can be scaled-up without much detrimental effects. In the field of polymers synthesis, this technology has been much less investigated, thus MAPS is being implemented in our laboratory as a key feature for the synthesis of different polymers and the modification of macromolecules. In this context, the polymerization times have been reduced from 2.5 hours (conventional thermal method) to 10-20 minutes. Different amphiphiles with a broad spectrum of molecular weights and hydrophilic/hydrophobic balances (given by the relations PEG/PCL) have been synthesized. The polymers are being fully characterized by different techniques.