Self-organizing nanoparticles based on drug-interpolyelectrolyte complexes loading with acidic drugs.

PALENA, MC.; GARCÍA, MC.; MANZO, RH.; JIMENEZ KAIRUZ, AF.

Rósario

Congreso; 2ra. Reunión Internacional de Ciencias Farmacéuticoas RICiFa 2012.; 2012

Universidad Nacional de Rosario

Introduction In the field of drug delivery, aqueous dispersions as well as hydrophilic matrices of polyelectrolyte-drug complexes (PE-D) have been extensively investigated1,2,3,4. Self-organized drug-interpolyelectrolyte complexes (DIPEC) can be obtained in aqueous dispersions by spontaneous association of oppositely charged polyelectrolytes due to strong but reversible electrostatic interactions5. The studies about their potential applications as nanoparticulate drug delivery systems are still limited6. Therefore, the aim of this study is the preparation of self-organized nanoparticles in aqueous dispersion based on DIPEC, the evaluation of physico-chemical properties and in vitro release performance to assess the potential utility of these systems in drug delivery. Materials and methods. Two anionic and cationic linear polymethacrylates derivatives, Eudragit®L100 (EL) and Eudragit®EPO (EE), respectively were selected as model counter polyelectrolytes. Benzoic acid (AB), salicylic acid (AS), ketoprofen (Ke) and naproxen (Nx) were selected as model drugs, upon consideration of their structures and acid-base behaviors. DIPEC with different EE-EL stoichiometric composition were prepared in aqueous dispersion by complex coacervation method. The influence of EE:EL ratio on turbidity (600 nm), pH, particle size distribution, electrokinetic potential (), were investigated. In addition the partition equilibrium 1,2-Dichloroethane:water (2:1) of D was measured in order to get the species distribution of DIPEC in aqueous. In vitro release studies in diffusion Franz cells, using water, 0.9% NaCl, pH 1.2 and 6.8 USP-buffer solutions as receptor media, were performed. The reversibility from solid state to aqueous dispersion and stability of dispersions stored at room temperature was assayed by dynamic light scattering. Result and Discussion Optical density of nanocomplex dispersions was significantly increased with proportions of EL-Na50 added. This effect can be related to the ionic interpolylectrolyte condensation (coacervation process). pH remained close to 5.0 even at the highest proportion of 100%. Under such conditions high and positive  were measured contributing to physical stability. This results suggest that the degree of ionization of EE amine groups remains higher than EL carboxylic groups. Surface charge became high and negative at pH  7. Partition equilibrium showed that a high proportion of D (up to 89%) is condensed with the PE under the form of ion pairs. DIPEC hydrodynamic diameters (dH) were in the range of 100 to 250 nm. Lyophilized samples of DIPEC, containing up to 50% of EL, were easily redispersed and both dH and  remained similar to those prepared in situ without any cryopreservative agent. On the other hand, no significant changes in  and dH were observed along 30 days. DIPEC exhibited a slow D release when water is the receptor medium. As water was replaced by NaCl 0.9 % as receptor medium, the release rates of the four drugs were significantly raised, promoted byo ionic exchange. Finally, nanocomplexes containing AS, AB, Ke showed similar release profiles under both simulated physiological media pH conditions. Naproxen release rate was slower in acidic medium. Conclusions Aqueous dispersions of a novel self-organized nanoparticulate carrier, based on DIPEC were prepared using a simple method. This complexes behave as a reservoir that slowly releases D in water. The release rate can be raised by ionic exchange. Besides they showed a remarkable robustness toward changes of pH of receptor media. The DIPEC systems exhibited interesting properties to design nanoparticulate drug delivery systems for oral and topical routes.