title: Mucoadhesive nanoparticles made of thiolated quaternary chitosan crosslinked with hyaluronan.
abstract: Mucoadhesive polymeric nanoparticles intended for drug transport across the gastrointestinal mucosa were prepared from quaternary ammonium-chitosan conjugates synthesised from reduced-MW chitosan (32 kDa). Conjugates contained pendant moieties of 2-4 adjacent diethyl-dimethylene-ammonium groups substituted on repeating units (26-55%). Conjugates were thiolated via amide bonds with thioglycolic acid to yield products with thiol content in the 35-87 μmol/g range. Nanoparticles with mean size in the 270-370 nm range and positive zeta-potential (+3.7 to +12.5 mV) resulted from ionotropic gelation of the thiolated conjugates with de-polymerised hyaluronic acid (470 kDa). The nanoparticles were fairly stable in size and thiol content and showed a significant mucoadhesivity, matching and even exceeding that of the constituent polymers. Nanoparticles were internalised by endothelial progenitor cells in direct relation to their surface charge intensity. Nanoparticle uptake significantly improved cell viability and resistance to oxidation. The lyophilised nanoparticles were re-dispersible and could make a manageable formulation for oral use.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy. zambito@farm.unipi.it
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Zambito
authors.forename: Francesca
authors.initials: F
authors.lastname: Felice
authors.forename: Angela
authors.initials: A
authors.lastname: Fabiano
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stefano
authors.forename: Giacomo
authors.initials: G
authors.lastname: Di Colo
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002686:Chitin / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D009092:Mucous Membrane / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties
chemical_list: D011108:Polymers; D002686:Chitin; D006820:Hyaluronic Acid; D048271:Chitosan