Abstract
The objective of this study was to develop and evaluate a hydrogel vehicle for sustained release of growth factors for wound healing applications. Hydrogels were fabricated using ultraviolet photo-crosslinking of acrylamide-functionalized nondegradable poly(vinyl alcohol) (PVA). Protein permeability was initially assessed using trypsin inhibitor (TI), a 21 000 MW model protein drug. TI permeability was altered by changing the solids content of the gel and by adding hydrophilic PVA fillers. As the PVA content increased from 10% to 20%, protein flux decreased, with no TI permeating through 20% PVA hydrogels. Further increase in model drug release was achieved by incorporating hydrophilic PVA fillers into the hydrogel. As filler molecular weight increased, TI flux increased. The mechanism for this is most likely an alteration in protein/gel interactions and transient variations in water content. The percent protein released was also altered by varying protein loading concentration. Release studies conducted using growth factor in vehicles with hydrophilic filler showed sustained release of platelet-derived growth factor (PDGF-β,β) for up to 3 days compared with less than 24 hours in the controls. In vitro bioactivity was demonstrated by doubling of normal human dermal fibroblas numbers when exposed to growth factor-loaded vehicle compared to control. The release vehicle developed in this study uses a rapid and simple fabrication method, and protein release can be tailored by modifying solid content, incorporating biocompatible hydrophilic fillers, and varying protein loading concentration.
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References
Steed DL. Clinical evaluation of recombinant human plateletderived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg. 1995;21(1):71–78.
Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled doubleblind study. Diabetes Care. 1998;21(5):822–827.
Margolis DJ, Crombleholme T, Herlyn M. Clinical protocol: Phase I trial to evaluate the safety of H5.020CMV.PDGF-B for the treatment of a diabetic insensate foot ulcer. Wound Repair Regen. 2000;8(6):480–493.
Arm DM, Tencer AF, Bain SD, Celino D. Effect of controlled release of platelet-derived growth factor from a porous hydroxyapatite implant on bone ingrowth. Biomaterials. 1996;17:703–709.
Kim HD, Valentini RF. Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-β delivered from controlled-release polymer rods. Biomaterials. 1997;18(17):1175–1184.
Lee JY, Nam SH, Im SY, et al. Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. J Control Release. 2002;78(1–3):187–197.
Walsh WR, Kim HD, Jong YS, Valentini RF. Controlled release of platelet-derived growth factor using ethylene vinyl acetate copolymer (EVAc) coated on stainless-steel wires. Biomaterials. 1995;16(17):1319–1325.
Lee SJ, Park YJ, Park SN, et al. Molded porous poly(L-lactide) membranes for guided bone regeneration with enhanced effects by controlled growth factor release. J Biomed Mater Res. 2001;55(3):295–303.
Park YJ, Ku Y, Chung CP, Lee SJ. Controlled release of platelet-derived growth factor from porous poly(L-lactide) membranes for guided tissue regeneration. J Control Release. 1998;51:201–211.
Park YJ, Lee YM, Lee JY, Seol YJ, Chung CP, Lee SJ. Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration. J Control Release. 2000;67(2–3):385–394.
Park YJ, Lee YM, Park SN, Sheen SY, Chung CP, Lee SJ. Platelet derived growth factor releasing chitosan sponge for periodontal bone regeneration. Biomaterials. 2000;21:153–159.
Zhou X, Zhao H. Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application. Acta Otolaryngol. 2002;122(6):586–599.
Richardson TM, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol. 2001;19:1029–1034.
Peppas NA, Wright SL. Drug diffusion and binding in ionizable interpenetrating networks from poly(vinyl alcohol) and poly(acrylic acid). Eur J Pharm Biopharm. 1998;46:15–29.
Hoffiman AS. Hydrogels for biomedical application. Adv Drug Deliv Rev. 2002;43:3–12.
Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov Today. 2002;7(10):569–579.
Gander B, Gurny R, Doelker E, Peppas NA. Effect of polymeric network structure on drug release from cross-linked poly(vinyl alcohol) micromatrices. Pharm Res. 1989;6(7):578–584.
Hennink WE, van Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2002;54:13–36.
Müller B. Photocrosslinked polymers. US patent 5 508 317. April, 16, 1996.
Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73(2–3):121–136.
Kök FN, Wilkins RM, Cain RB, Arica MY, Alaeddinoglu G, Hasirci V. Controlled release of aldicarb from lignin loaded ionotropic hydrogel microspheres. J Microencapsul. 1999;16:613–623.
Krögel I, Bodmeier R. Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder. J Control Release. 1999;61(1–2):43–50.
Sako K, Sawada T, Nakashima H, Yokohama S, Sonobe T. Influence of water soluble fillers in hydroxypropylmethylcellulose matrices on in vitro and in vivo drug release. J Control Release. 2002;81(1–2):165–172.
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Published: December 4, 2003
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Bourke, S.L., Al-Khalili, M., Briggs, T. et al. A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications. AAPS PharmSci 5, 33 (2003). https://doi.org/10.1208/ps050433
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DOI: https://doi.org/10.1208/ps050433