Three model drugs (insulin, diclofenac sodium, and salicylic acid) with different pI or pKa were used to prepare drug-chitosan micro/nanoparticles by ionic interaction. Physicochemical properties and entrapment efficiencies were determined. The amount of drug entrapped in the formulation influences zeta potential and surface charge of the micro/nanoparticles. A high entrapment efficiency of the micro/nanoparticles could be obtained by careful control of formulation pH. The maximum entrapment efficiency did not occur in the highest ionization range of the model drugs. The high burst release of drugs from chitosan micro/nanoparticles was observed regardless of the pH of dissolution media. It can be concluded that the ionic interaction between drug and chitosan is low and too weak to control the drug release.