CPA-loaded polymeric nanoparticles prepared via a non-aqueous nanoprecipitation method

Purpose: A novel non-aqueous nanoprecipitation method was used to achieve the encapsulation of a small weight hydrophilic drug (N6-cyclopentyladenosine, CPA) in PLA or PLGA nanoparticles. The drug release properties and the size characteristics of nanoparticles were investigated. Methods: Nanoparticles were prepared by a nanoprecipitation method using an organic solvent in the presence of Tween 80. The obtained nanoparticles were purified by ultrafiltration, suspended in water by sonication and freeze-dried. The release studies were performed in water and drug stability was evaluated in physiologic fluids. Results: The freeze-dryed nanoparticles re-dispersed by sonication produced a monodispersed colloidal system. The drug loading capability obtained by this technique appeared considerably higher than that found by the conventional encapsulation methods. Using either PLA or PLGA polymer, a biphasic drug release profile was observed. The extent of the first burst release was dependent on the initial amount of drug in the preparation. The second release phase was slow and characterized by a probable diffusion mechanism. The rate of the second drug release phase can be accelerated or retarded by the presence of a filler (such as lauric acid) or a pore former agent (such as Tween 20), respectively. Conclusions: The novel method used allows an efficient drug loading to be obtained along with a prolonged drug release, despite the small size of the nanoparticles and the hydrophilic nature of the drug. The most interesting feature of this novel method is not only the possibility to produce high loaded nanoparticles but also modulate their drug release rate