title: Composite nanoparticles based on hyaluronic acid chemically cross-linked with alpha,beta-polyaspartylhydrazide.
abstract: In this paper, new composite nanoparticles based on hyaluronic acid (HA) chemically cross-linked with alpha,beta-polyaspartylhydrazide (PAHy) were prepared by the use of a reversed-phase microemulsion technique. HA-PAHy nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence of the chemical cross-linking, dimensional analysis, and transmission electron micrography, showing a sub-micrometer size and spherical shape. Zeta potential measurements demonstrated the presence of HA on the nanoparticle surface. A remarkable affinity of the obtained nanoparticles toward aqueous media that simulate some biological fluids was found. Stability studies showed the absence of chemical degradation in various media, while in the presence of hyaluronidase, a partial degradation occurred. Cell compatibility was evaluated by performing in vitro assays on human chronic myelogenous leukaemia cells (K-562) chosen as a model cell line and a haemolytic test. HA-PAHy nanoparticles were also able to entrap 5-fluorouracil, chosen as a model drug, and release it in a simulated physiological fluid and in human plasma with a mechanism essentially controlled by a Fickian diffusion.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi, 32-90123 Palermo, Italy. giopitar@unipa.it
authors.forename: G
authors.initials: G
authors.lastname: Pitarresi
authors.forename: E F
authors.initials: EF
authors.lastname: Craparo
authors.forename: F S
authors.initials: FS
authors.lastname: Palumbo
authors.forename: B
authors.initials: B
authors.lastname: Carlisi
authors.forename: G
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D004867:Equipment Design; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid; D006834:Hydrazines / Q000737:chemistry*; D006868:Hydrolysis; D020014:K562 Cells; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry*; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D006834:Hydrazines; D009757:Nylons; C114303:alpha,beta-polyasparthydrazide; D006820:Hyaluronic Acid; D005472:Fluorouracil