Journal
MOLECULAR PHARMACEUTICS
Volume 11, Issue 5, Pages 1599-1610Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp400774v
Keywords
drug delivery system; hollow microspheres; layer-by-layer assembly; pH-sensitive fluorescence; hepatocyte targeting; controlled release
Funding
- National Nature Science Foundation of China [20904017]
- Program for New Century Excellent Talents in University [NCET-09-0441]
- Chunhui Project from the Ministry of Education of China [Z2012116]
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Novel multilayer polyelectrolyte hollow microspheres with pH-sensitive fluorescence and hepatocyte-targeting functions were successfully fabricated via a layer-by-layer (LbL) assembly of fluorescein isothiocyanate (FITC)-modified chitosan (CSFITC) and sodium hyaluronate (HA) (as the polycation and polyanion, respectively) on polystyrene sulfonate (PSS) templates with galactosylated chitosan (GC) as the outermost layer; after etching the templates by dialysis, the aim was to use the microspheres to target hepatocytes specifically. TEM analysis revealed that they have a hollow structure with a particle size of about 260 nm, and DLS analysis demonstrated that they have pH and ionic strength dual-responsive characteristics. The hollow microspheres showed pH-sensitive fluorescence at a very low concentration by fluorescent emission spectra. MTT assays revealed that doxorubicin (a water-insoluble anticancer drug)-loaded (CSFITC/HA)(4)/GC hollow microspheres can specifically target hepatocytes and exhibit favorable cytocompatibility. Three typical model drugs were loaded into the (CSFITC/HA)(4)/GC hollow microspheres, and their drug-release kinetics in simulated body fluid (SBF) were estimated with different mathematical models. The results demonstrated that the drug-loading mechanism is chemosorption and the primary governing force for drug release is diffusion. Thus, the designed hollow microspheres are expected to be used for the diagnosis and therapy of hepatic cancer.
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