title: Stability and ocular tolerance of cyclophosphamide-loaded nanospheres.
abstract: The physical and chemical stabilities of several formulations of cyclophosphamide-loaded polybutylcyanoacrylate (PBCA) nanospheres developed for an ophthalmic application as an immunosuppressive agent were studied over 6 months of storage at 4, 25 and 40 degrees C in different experimental conditions. The physical stability of nanospheres was followed by the study of morphological (visual appearance) and morphometrical properties (mean particle size and polydispersity). The pH and tonicity of the suspensions and the association efficiency of the drug to polymeric system were also analysed to evaluate their chemical stability. The behaviour of colloidal suspensions with storage conditions was also followed by differential scanning calorimetry. The degradation of PBCA was affected by temperature and pH. The average particle size of all nanospheres remained practically unchanged throughout the study, with the polydispersity index being less than 0.1, corresponding to a monodisperse system. At 40 degrees C, a loss of 25.9% of the initial association efficiency, especially in non-buffered pH 7.2 medium, was observed. The type of polymer degradation (surface erosion) was also determined by photon correlation spectroscopy. The results obtained from in vivo study of ocular tolerance indicate a good ocular tolerance for drug loaded to nanospheres.
authors.affiliation: Physicochemistry Department, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n. E-08028 Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Salgueiro
authors.forename: M A
authors.initials: MA
authors.lastname: Egea
authors.forename: M
authors.initials: M
authors.lastname: Espina
authors.forename: O
authors.initials: O
authors.lastname: Valls
authors.forename: M L
authors.initials: ML
authors.lastname: García
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003520:Cyclophosphamide / Q000494:pharmacology; D004355:Drug Stability; D004659:Enbucrilate; D005123:Eye / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000494:pharmacology; D043942:Nanotubes; D010316:Particle Size; D011817:Rabbits; D013696:Temperature
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D004659:Enbucrilate