Immobilization of basic fibroblast growth factor on heparin/EDC-methiodide nano-aggregates to maintain its continuous signaling

In this study, we designed heparin/1-(3′-dimethylaminopropyl)-3-ethylcarbodiimide methioide (Hep/EDC) nanoaggregates (NAs) for basic fibroblast growth factor (bFGF) delivery carrier. The Hep/EDC NAs was formed by electrostatic interaction between negatively charged functional groups in heparin and positively charged EDC. In the formed Hep/EDC NAs, the size (148–303 nm) and surface charge (positive or negative) were controlled by Hep/EDC ratio. Then, we investigated the effect of two different bFGF loaded Hep/EDC NAs on maintenance of bFGF activity. The two strategies for loading bFGF into the Hep/EDC NAs were physical encapsulation and physicochemical immobilization. The bFGF was physically incorporated into Hep/EDC NAs by binding with heparin which has the high affinity of bFGF and it was chemically conjugated to Hep/EDC NAs by amide bonding. The bFGF was released more slowly from bFGF-conjugated Hep/EDC NAs than bFGF-encapsulated Hep/EDC NAs. Finally, we obtained the sustained level of bFGF until 5 days in physiological conditions by bFGF-immobilized HEP/EDC NAs, resulting in more effective cell proliferation as compared with same amount of Hep and bFGF. We suggest that this approach will provide one way to design carriers for controlled delivery of chemotherapeutic agents including bFGF with maintenance of their mitogenic and chemotactic activity.