Fabrication of Biocompatible and Tumor‐Targeting Hyaluronan Nanospheres by a Modified Desolvation Method. Issue 5 (6th March 2014) - Zheng, Wenyi
Abstract 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 J Pharm Sci 103:1529–1537, 2014