Fabrication of Biocompatible and Tumor-Targeting Hyaluronan Nanospheres by a Modified Desolvation Method

The aim of this work was to maximize the tumor targetability of biocompatible hyaluronan (HA) by construction of a novel nanocarrier, using HA as the single material. HA was prefunctionalized with active amino groups, desolvated by acetone, and cross-linked by glutaraldehyde. The process was further optimized with regard to yield, stability, and particle size. The cytotoxicity of HA nanospheres (HA-NPs) was evaluated by thiazolyl blue tetrazolium bromide and reactive oxygen species assays. A549 cells and H22-bearing Kunming mice were employed to characterize the tumor targeting of fluorescein isothiocyanate-conjugated HA-NPs. Nanospheres prepared according to the optimal formulation were characterized by a maximum yield (90%), high stability over 7 days, regular spheres (97.42 nm in diameter), and negative charge (−32.7 mV in zeta potential). In vitro results revealed that HA-NPs had little cytotoxicity and efficiently accumulated into A549 cells in a HA-dependent manner. Following systemic administration in mice, HA-NPs selectively accumulated in the tumor as demonstrated by the frozen section examination and flow cytometry analysis. In conclusion, this work successfully prepared HA-NPs and explored their potential applications for tumor targeting in terms of safety and efficacy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.