6533b86ffe1ef96bd12ce9e1
RESEARCH PRODUCT
Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins
Gennara CavallaroSalvatore Emanuele DragoEmanuela Fabiola CraparoRobert Luxenhofersubject
Poly(2-oxazoline)sPolymers116 Chemical sciencesPharmaceutical ScienceMedicine (miscellaneous)Nanoparticle02 engineering and technology01 natural scienceschemistry.chemical_compoundDrug Delivery SystemsNanoparticlePolylactic acidCopolymerPolyaminesHydroxyureaGeneral Materials SciencePoly(2-oxazine)sDRUG-DELIVERYCells Culturedchemistry.chemical_classificationDrug CarriersCHALLENGESAIRWAY MUCUSPolymer021001 nanoscience & nanotechnologyGraftingDIFFUSIONPolyaspartamidePULMONARY DELIVERYDrug deliveryMolecular Medicine0210 nano-technologyHydrophobic and Hydrophilic Interactionsmedicine.drugLung inflammationPolyestersBiomedical EngineeringINHIBITIONBioengineeringBronchi010402 general chemistryPolylactic acidZileutonAmphiphileAdministration InhalationmedicineHumansPoly(2-oxazoline)RELEASEMucinsBronchial DiseasesEpithelial CellsZileuton0104 chemical scienceschemistryChemical engineeringSettore CHIM/09 - Farmaceutico Tecnologico ApplicativoNanoparticlesASTHMAPoly(2-oxazine)description
In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24hours. Peer reviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-10-01 |