title: Fabrication of biocompatible and tumor-targeting hyaluronan nanospheres by a modified desolvation method.
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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Zheng
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Li
authors.forename: Jinping
authors.initials: J
authors.lastname: Du
authors.forename: Zongning
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size
chemical_list: D004337:Drug Carriers; D006820:Hyaluronic Acid
keywords: CD44; cancer; desolvation; drug targeting; hyaluronan; nanospheres; polymeric drug delivery systems