Biodegradable micelles from a hyaluronan-poly(ε-caprolactone) graft copolymer as nanocarriers for fibroblast growth factor 1

A novel copolymer (HA-g-PCL) was prepared by grafting hydrophobic poly(epsilon-caprolactone) (PCL) chains onto the backbone of hydrophilic hyaluronic acid (HA) with a grafting ratio of similar to 7%. The copolymer formed micelles with a size of similar to 60 nm in aqueous solution over a critical concentration of similar to 4 mu g mL(-1). Each micelle consisted of about four copolymer chains. Fibroblast growth factor 1 (FGF1) may be encapsulated in micelles by various methods. In particular, FGF1 loaded to micelles through 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) conjugation provided efficient (similar to 87%) and large amount (up to similar to 175 mu g FGF1 per mg HA-g-PCL, or on average one FGF1 molecule per micelle) of loading as well as reduced burst release of FGF1. FGF1-loaded micelles remained functional after 21 days. Experimental rats receiving FGF1-loaded micelles showed better wound contraction and faster sebaceous gland formation than those receiving free FGF1 or empty micelles. We conclude that novel HA-g-PCL micelles are good nanocarriers for the controlled release of FGF1 and may be applied to encapsulate other bioactive molecules for therapeutic purposes.