Preparation of aspirin and probucol in combination loaded chitosan nanoparticles and in vitro release study

Abstract

We design and develop chitosan nanoparticles which load two different drugs simultaneously. Aspirin (acetylsalicylic acid, ASA), a hydrophilic drug and probucol (PRO), a hydrophobic drug, are chosen as typical drugs, which are widely used to treat restenosis. The drug loaded chitosan nanoparticles are prepared by gelation of chitosan with tripolyphosphate (TPP) by ionic cross-linking. The physicochemical properties of nanoparticles are investigated by FTIR, transmission electron microscope (TEM), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The images show that these particles are spherical in shape with ASA being in the amorphous phase, while PRO is crystalline. The properties of chitosan nanoparticles such as encapsulation capacity and controlled release behaviors of ASA and PRO are evaluated. Experimental results indicate that the loading capacity (LC), encapsulation efficiency (EE) and ASA and PRO release behaviors are affected by several factors including pH, concentration of TPP, chitosan molecular weight (MW) and ASA initial concentration as well as PRO. In vitro release shows that the nanoparticles provide a continuous release. Entrapped ASA is released for more than 24 h and PRO lasts longer for 120 h.