Abstract
Although hydrogels are widely used in controlled-release systems, obtaining extended, uniform drug release with little initial burst has been challenging. However, recently researchers have shown that combining hydrogels with another drug delivery material can dramatically improve release kinetics. Here we describe a novel hydrogel-based composite material that exhibits stable, near-linear, sustained release of a model hydrophilic protein (e.g., bovine albumin serum, BSA) for over two months with a significant reduction in initial burst release (7% vs. 20%). The composite is comprised of poly(ε-caprolactone) (PCL) electrospun fiber mats coupled with poly(ethylene glycol)-poly(ε-caprolactone) diacrylate (PEGPCL) hydrogels through photo-polymerization. It is believed that the additional diffusion barrier provided by hydrophobic electrospun fiber mats reduces hydrogel swelling and water penetration rates and increases the diffusion path length, resulting in delayed, more uniform drug release. Further, released proteins remain bioactive as demonstrated by PC12 cell neurite extension in response to released nerve growth factor (NGF). The use of electrospun fiber mats to modulate hydrogel drug release provides a new method to control release kinetics of hydrophilic proteins, reducing burst release and extending the release duration.
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