title: Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network.
abstract: Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10(5), 1.26 ± 0.43 × 10(5), 0.96 ± 0.09 × 10(5), 0.64 ± 0.03 × 10(5), and 0.11 ± 0.01 × 10(5) respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously.
authors.affiliation: Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China. Electronic address: jhzhao@jnu.edu.cn.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Rong
mesh_terms: D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005782:Gels / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D008027:Light; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013455:Sulfur / Q000032:analysis; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005782:Gels; D014867:Water; D012710:Serum Albumin, Bovine; D013455:Sulfur; D006820:Hyaluronic Acid
keywords: Crosslink density; Hyaluronan; Microgel; Protein; Sustained delivery