GARCÍA MÓNICA CRISTINA
Congresos y reuniones científicas
Título:
Novel controlled release hydrogels formulation based on dendritic anionic polyelectrolyte-ciprofloxacin complexes
Autor/es:
MÓNICA CRISTINA GARCÍA; CUGGINO, JULIO C.; ALVAREZ-IGARZABAL, CECILIA; RUBEN HILARIO MANZO; ALVARO FEDERICO JIMENEZ-KAIRUZ
Lugar:
Rosario, Santa Fé
Reunión:
Congreso; 2° Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2012
Institución organizadora:
Universidad Nacional de Rosario - Universidad Nacional de Córdoba
Resumen:
Introduction Hydrogels are three-dimensional, cross-linked networks of water soluble polymers. A particular class of hydrogels is based on drug-polyelectrolite (D-PE) complexes, where a molecular dispersion of D is ionically bounded at the ionizable groups of PE (1-4). The unique phisical properties of these hydrogels place them as interesting systems to be used en controlled D delivery (5). Recently, a new anionic dendritic polylelectrolyte (DP) was synthesized by aqueous free-radical polymerization of a particularly prepared vinyl monomer derivate from Behera´s amine (6). In previous work, DP was considered as a potential non toxic material (7). Its complexes with Ciprofloxacin (Cip) showed acceptable microbiological activity versus Staphylococcus aureus y Pseudomona aeruginosa (8). This work is based on the evaluation of DP as a carrier of the antimicrobial Cip with potential use in topical and mucosal administration. Cip was selected as ionizable model drug because of its wide use in common topical opportunist infections. Materials and Methods A series of DPx, where ?x? is the DP crosslinking degree were obtained by the addition of 0.5, 2 and 4 mol% (+)-N, N´-diallyltartramide. They were used to obtain DP-CIP complexes by ionic reaction in solid state in which free base Cip neutralized 25% of the acid groups of DP. The mixture of DP and Cip was mixing with appropriate volume of ethanol to obtain a semisolid paste of DPx-Cip25. The complexes were kept at room temperature for 24 h and dried until constant weight at 40 °C. The solid complexes were characterized by spectroscopic, calorimetric, crystallographic and rheological techniques (FTIR, DSC/TG, DRXP, optical microscopy and oscillatory rheology). To obtain the hydrogels, the complexes DP-Cip25 were dispersed in distilled water with an appropriate amount of 1M NaOH which neutralized 20% of the acid groups of DP. In vitro release studies in diffusion Franz cells from DP-Cip25-Na20 hydrogel were performed where the receptor compartment was filled with water, 0.9% NaCl, pH 6.8 USP-buffer solution. Results FTIR, DXRP, DSC and optical microscopy analysis showed ionic interaction between DP and Cip in DPx-Cip25 complexes. Opaque and stable DP-Cip25-Na20 viscous hydrogels (pH in the range of 6.2 to 6.8) were obtained. Viscoelastic measurement showed predominant storage moduli, that was increased with the DP crosslinking degree. Hydrogels exhibited a slow release of Cip towards water. As water was replaced by NaCl solution release rate raised significantly (3 to 5 times). An intermediate behavior was observed when buffer solution was in the receptor compartment. Release profiles were fitted to Peppas equation and not significant differences were observed among the different cross-linking grades (p>0.05). Discussion and conclusions New controlled release systems based on DP-Cip were developed. The DP-Cip25-Na20 hydrogels were physically stable, biocompatible and behaves as a reservoir of Cip. In addition, they showed acceptable microbiological activity. These systems showed promising properties that could be exploited for topical and mucosal drug administration. Acknowledgement This work was supported by SECyT-UNC, FONCyT and CONICET. References 1. Jimenez-Kairuz AF, Allemandi DA, Manzo RH (2002) Mechanism of lidocaine release from Carbomer-lidocaine hydrogels. J Pharm Sci 91:267?272. 2. Ardusso MS, Manzo RH, Jimenez-Kairuz AF (2010) Comparative study of three structurally related acid polyelectrolytes as carriers of basic drugs: carbomer, eudragit L-100and S-100. Supramol Chem 5:289?296. 3. Quinteros DA, RamirezRigo MV, Jimenez-Kairuz AF, OliveraME, Manzo RH, Allemandi DA (2008) Interaction between a cationic polymethacrylate (eudragit E100) and anionic drugs. Eur J Pharm Sci 33:72?79 4. Quinteros DA, Manzo RH, Allemandi DA (2011) Interaction between eudragit_ E100 and anionic drugs: addition of anionic polyelectrolytes and their influence on drug release performance. J PharmSci 100(11):4664?4673. doi:10.1002/jps.22651. 5. Hoare TR., Kohane DS. 2008. Hydrogels in drug delivery: Progress and challenges. Polymer, 49: 1993-2007. 6. Cuggino JC., Calderón M., Alvarez CI., Strumia MC., Silva KN., Penott-Chang EK., Müller AJ., 2011. New dendronized polymers from acrylate Behera amine and their ability to produce visco-elastic structured fluids when mixed with CTAT worm-like micelles. Journal of Colloid and Interface Science 357 (2011) 147-156. 7. International standars ISO 10993-5. Biological evaluation of medical devices. Part 5: Tests for in vitro cytotoxicity. Thirth edition ed. 2009. 8. García MC., Cuggino J., Rosset C., Manzo R., Alovero F., Álvarez Igarzabal C., Jimenez-Kairuz A. 2012. Evaluación de nuevo polímero dendrítico como potencial sistema portador de antimicrobianos. Reunión Anual SAFE-2012, Mendoza, Arg.