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Pharmaceutical Research, Vol. 26, No. 9, September 2009 (# 2009) DOI: 10.1007/s11095-009-9923-1
Research PaperDrug Release Kinetics and Transport Mechanisms from Semi-interpenetrating
Networks of Gelatin and Poly(ethylene glycol) diacrylate
Yao Fu,1 and Weiyuan John Kao1,2,3
Received March 23, 2009; accepted June 3, 2009; published online June 25, 2009
Purpose. To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading density have been investigated.
Materials and Methods. sIPNs of following gelatin/PEGdA weight-to-weight ratios were prepared: 10:15, 10:20, 10:30, 15:15, 20:15. Five model solutes of different physicochemical properties were selected, i.e. silver sulfadiazine (AgSD), bupivacaine hydrochloride (Bup), sulfadiazine sodium (NaSD), keratinocyte growth factor (KGF), and bovine serum albumin conjugated with uorescein isothiocyanate (BSAFITC). Release studies were performed and the results were analyzed using three hydrogel based common theories (free volume, hydrodynamic and obstruction).
Results. The release kinetics of model solutes was inuenced by each factor under investigation. Specically, the initial release rates and intra-gel diffusivity decreased with increasing PEGdA content or increasing solute molecular weight. However, the initial release rate and intra-gel diffusivity increased with increasing gelatin content or increasing solute water solubility, which contradicted with the classical hydrogel based solute transport theories, i.e. increasing polymer volume leads to decreased solute diffusivity within the gel.
Conclusion. This analysis provides structure-functional information of the sIPN as a potential therapeutic delivery matrix.
KEY WORDS: diffusion; gelatin; poly(ethylene glycol) diacrylate; semi-interpenetrating network.
INTRODUCTION
A semi-interpenetrating network (sIPN) comprised of photocrosslinked poly(ethylene glycol) diacrylate (PEGdA) and a naturally derived macromolecule gelatin has been developed (1). Designed for wound healing, the sIPNs are photocrosslinked in situ under physiological conditions, enabling complete wetting of the wound bed, even in the presence of complex 3-D topography (2). sIPNs are distinguishable from blends, block copolymers, and graft copolymers in two ways: rstly, the sIPN swells but does not dissolve in solvents, and secondly, creep and ow are suppressed (3). Bearing similarities to hydrogels, such as crosslinked matrices, high water capacity, and swelling ability, the sIPN system is only partially crosslinked, which makes it more complex, more heterogeneous and less rigid than classical hydrogel systems. Previous studies revealed that the sIPN...