Microdialysis for evaluating the entrapment and release of a lipophilic drug from nanoparticles

The aim of the study was to evaluate the microdialysis (MD) as a tool to determine entrapment efficiency and drug release of a lipophilic drug model, diclofenac (DIC), from nanocapsules, nanospheres, and nanoemulsions. Factors that could interfere with the MD probe recovery were investigated: perfusion fluid composition, concentration and form of the drug in the perfusate, and recovery method. DIC entrapment efficiency to nanoparticles and the drug release in phosphate buffer pH 7.4 after different dilutions were evaluated by MD and ultrafiltration/centrifugation (UC). DIC recovery for the 5 muL/min flux was concentration and pH dependent. DIC sodium was used for the recoveries determination since it did not differ from the DIC acid recovery for the same media. DIC entrapment efficiency determined applying both techniques were equivalent and close to 100% for all nanoparticles. In pH 7.4 DIC release from the nanoparticles was partial for the dilution rate 1:1 (v/v), around 50-60%. A complete release was observed from 1:10 (v/v) dilution. Only nanocapsules presented a incomplete release for 1:5 (v/v) dilution, around 86%. MD and UC techniques were equivalent for the evaluation of DIC entrapment efficiency and drug release from the nanoparticles. (C) 2004 Elsevier B.V. All rights reserved.