title: Biodegradable micro- and nanoparticles as long-term delivery vehicles for interferon-alpha.
abstract: The development of new interferon-alpha (IFN-alpha) delivery strategies is a key issue in order to simplify its administration and improve its therapeutic effects, while reducing its dose-related side effects. One of the most attractive approaches towards this aim is the encapsulation of IFN-alpha into poly(lactic-glycolic acid) (PLGA) microspheres. Nevertheless, the stability of IFN-alpha released from these microspheres has been identified as one of the most important concerns in relation to the potential of this approach. Being conscious of this problem, we have used new strategies for the encapsulation of IFN-alpha into biodegradable micro- and nanoparticles. We chose poloxamer 188 as a stabilizing agent and encapsulated IFN-alpha within PLGA/poloxamer blend microspheres prepared by an oil-in-oil solvent extraction technique and also within PLGA micro- and nanospheres containing poloxamer, prepared by the water-in-oil-in-water solvent evaporation technique. The results showed that these techniques led to the efficient encapsulation of IFN-alpha and the modulation of their particle size, ranging from nanospheres (280 nm) to 40 microm-microspheres. These systems exhibit a similar pattern of release that is characterized by an initial burst (2-24% IFN-alpha released, as determined by ELISA) followed by small pulses of immunoenzymatically detected IFN-alpha for up to 1 month. The maintenance of the structural integrity and bioactivity of the protein was confirmed using a cytostasis bioassay. The results showed that the antiproliferative activity of the IFN-alpha varied depending on the formulation. More specifically, PLGA/poloxamer blend microspheres were able to provide significant amounts of active IFN-alpha for up to 96 days. This new IFN-alpha delivery system opens up possibilities to improve present IFN-alpha-based therapies.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sánchez
authors.forename: María
authors.initials: M
authors.lastname: Tobío
authors.forename: Libia
authors.initials: L
authors.lastname: González
authors.forename: Angels
authors.initials: A
authors.lastname: Fabra
authors.forename: María J
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D001673:Biodegradation, Environmental; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D008863:Microspheres; D043942:Nanotubes; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D016898:Interferon-alpha; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid