title: Is dialysis a reliable method for studying drug release from nanoparticulate systems?-A case study.
abstract: The kinetics of in vitro drug release from nanoparticulate systems is extensive, though uncritically, being studied by dialysis. Evaluating the actual relevance of dialysis data to drug release was the purpose of this study. Diclofenac- or ofloxacin-loaded chitosan nanoparticles crosslinked with tripolyphosphate were prepared and characterized. With each drug, dynamic dialysis was applied to nanoparticle dispersion, solution containing dissolved chitosan·HCl, and solution of plain drug. Drug kinetics in receiving phase (KRP), nanoparticle matrix (KNM) and nanoparticle dispersion medium (KDM) were determined. Release of each drug from nanoparticles was also assessed by ultracentrifugation. Although KRP data may be interpreted in terms of sustained release from nanoparticles, KNM and KDM data show that, with both drugs, the process was in fact controlled by permeation across dialysis membrane. Analysis of KRP data reveals a reversible interaction of diclofenac with dispersed nanoparticle surface, similar to the interaction of this drug with dissolved chitosan·HCl. No such interactions are noticed with ofloxacin. The results from the ultracentrifugation method agree with the above interpretation of dialysis data. This case study shows that dialysis data from a nanoparticle dispersion is not necessarily descriptive of sustained-release from nanoparticles, hence, if interpreted uncritically, it may be misleading.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy. zambito@farm.unipi.it
authors.forename: Y
authors.initials: Y
authors.lastname: Zambito
authors.forename: E
authors.initials: E
authors.lastname: Pedreschi
authors.forename: G
authors.initials: G
authors.lastname: Di Colo
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D003956:Dialysis / Q000379:methods*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D007700:Kinetics; D053758:Nanoparticles; D015242:Ofloxacin / Q000008:administration & dosage / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods; D014461:Ultracentrifugation
chemical_list: D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011122:Polyphosphates; D004008:Diclofenac; D048271:Chitosan; D015242:Ofloxacin; C005692:triphosphoric acid