title: Biodegradable Janus nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs.
abstract: The aim of the present work is to synthesize, characterize, and test self-assembled anisotropic or Janus particles designed to load anticancer drugs for lung cancer treatment by inhalation. The particles were synthesized using binary mixtures of biodegradable and biocompatible materials. The particles did not demonstrate cyto- and genotoxic effects. Janus particles were internalized by cancer cells and accumulated both in the cytoplasm and nuclei. After inhalation delivery, nanoparticles accumulated preferentially in the lungs of mice and retained there for at least 24 h. Two drugs or other biologically active components with substantially different aqueous solubility can be simultaneously loaded in two-phases (polymer-lipid) of these nanoparticles. In the present proof-of-concept investigation, the particles were loaded with two anticancer drugs: doxorubicin and curcumin as model anticancer drugs with relatively high and low aqueous solubility, respectively. However, there are no obstacles for loading any hydrophobic or hydrophilic chemical agents. Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer. In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors. It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey University , 160 Frelinghuysen Rd., Piscataway, New Jersey 08854, United States.
authors.forename: Olga B
authors.initials: OB
authors.lastname: Garbuzenko
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winkler
authors.forename: M Silvina
authors.initials: MS
authors.lastname: Tomassone
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016880:Anisotropy; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001692:Biological Transport; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008168:Lung / Q000378:metabolism*; D051379:Mice; D009152:Mutagenicity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin; D003474:Curcumin