Group Members:John Byce (Co-Leader), Alex Johnson (BSAC) , Sarah Reichert (Co-Leader), Jeff Hlinka (BWIG), Anthony Sprangers (Communicator)Advisor: Professor Chris BraceClient: Dr. Neil Barney Dry Eye affects 10 million Americans Chronic, incurable disease Available treatments only for comfort Growth factors for comfort and renewal“A polymeric networks with 3D configuration capable of imbiding high amounts of water or biological fluids.” Absorbs because of hydrophilic groups Structure resembles body tissue http://www.pharmainfo.net/devisarvani/hydrogels-novel-drug-delivery-systemHamidi, M., Azadi, A., & Rafiei, P. (2008). Hydrogel nanoparticles in drug delivery.Advanced Drug Delivery Reviews, 60(15), 1638-1649.Intrinsic ExtrinsicDry Eye Aqueous Deficient Dry Eye (ADDE) Evaporative Dry Eye (EDE) Sjögren Sydrome Non-Sjögren Sydrome2º1º Age-RelatedOtherEpithelial Cell DestructionInflammationADDE and EDEIrritation and other Dry Eye symptomsTear HyperosmolarityTear Film Instability Tear Supplementation Tear Secretagogues Tear Retentiono Punctal Occlusiono Contact Lenseshttp://www.parkavenuelaser.com/images/punctalplugs.jpg Anti-inflammatory therapyo Cyclosporineo Corticosteroids Biological tear substituteso Serumo Salivary Gland Autotransplantationhttp://www.latisse.com/images/restasis.jpghttp://www.bausch.ca/en_CA/images/product_full_img/pharma/lotemax_lg_en.www.oasismedical.com Pros◦ Protein: Most abundant◦ Natural: Non-antigenic◦ Biodegradable, bioreabsorbable, biocompatible◦ History Cons◦ Variability of properties◦ Hydrophilicity◦ Ergonomics Cross-Linking◦ Glutaraldehyde, chromium tanning◦ Entrapment◦ Increases durability, dissolving rate, drug release rate and drug contact time Degradation process◦ Breakdown cross-linked proteins◦ Surface layer replenished◦ Incorporation of EGF, possible other drugsPolyoxyethylene (EO) and Polyoxypropylene (PO) triblock copolymer.http://www.uspbpep.com/usp28/v28230/usp28nf23s0_m66210.htm C2H4O – EO Block• HydrophilicC3H6O – PO Block• Hydrophobic Thermo-reversible property varies with concentration FDA considers inactive ingredient Gel dissolution < 12 hoursTemp ↑ Temp ↑ PO BlockEO BlockA review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics”, Pharmaceutical Research, Vol. 23, No. 12, December 2006. Photocross-links not readily degradable Dithiol bridges are hydrolytically labile Varying ratio alters extent of degradationhttp://www.nibib.nih.gov/Research/ResourceCenters/ListStatehttp://www.nibib.nih.gov/nibib/image/Research/P41Images/MToner_cellarray.jpgEGFEGF EGFEGFEGFEGFEGFPOLY(ETHYLENE GLYCOL) GELEPIDERMALGROWTHFACTORPoly(ethyleneglycol) Gel Poloxamer407 GelCollagenShieldBiocompatibility (25pts)202025Degradation Control (25 pts)251520Cost of Materials (5 pts)552Ergonomics (15 pts)101510Drug Release Control (30 pts)251020Total857077Epidermal Growth Factor Molecular weight of 6000 Da Differentiation and proliferation of epithelial cells Chain contains 53 amino acidsAdditional Growth Factors Insulin-Like Growth Factor-1 (IGF-1) Substance PCorneal wound in presenting patientHealed corneal wound after weeks treatment of IGF-1 and Sub PBarney, N. P., MD. (2002). Substance P, insulinlike growth factor 1, and surface healing.Clinicopathologic Reports, Case Reports, and Small Case Series, 120(FEB 2002), 215-216.EGF EGF EGFEGFEGFEGFEGFIGF-1IGF-1IGF-1INSULIN-LIKEGROWTHFACTOR-1POLY(ETHYLENE GLYCOL) GELEPIDERMALGROWTHFACTORItemCostEpidermal Growth Factor$180 for 1mgInsulin-Like Growth Factor-1$150 for 1mgSubstance P$75 for 1mgTotal$180 ($405) Testing◦ Gel degradation Wet mass (initial) Dry mass – freeze drying◦ Drug release Release of Methyl Blue tested by spectrometer Growth factor in human corneal epithelial cell cultures Gel additives◦ Cell adhesion ligand◦ Drug delivery vehicle Alginate microsphereshttp://www.uic.edu/classes/bios/bios100/f06pm/lect06.htm Pharmacopeia Online, “Poloxamer”, [Online] available at http://www.uspbpep.com/usp28/v28230/usp28nf23s0_m66210.htm , [Accessed 25 Feb 2010] G. Dumortier, J. Grossiord, F. Agnely, and J. Chaumeil, “A review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics”, Pharmaceutical Research, Vol. 23, No. 12, December 2006. E. Kim, Z. Gao, J. Park, H. Li, and K. Han, “rhEGF/HP-β-CD complex in poloxamer gel ophthalmic delivery”, InternationalJournal of Pharmaceutics, Vol. 233, Issues 1-2, 21 February 2002, pp 159-167. G. Niu et al., “Synthesis and characterization of reactive Poloxamer 407s for biomedical applications”, Journal ofControlled Release, Vol. 138, 2009, pp 49-56. Cosmetic Ingredient Review Expert Panel, “Safety Assessment of Poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, 407, Poloxamer105 Benzoate, and Poloxamer 183 Dibenzoate as used in Cosmetics”, International Journal of Toxicology, 2008, Vol. 27, pp 93-128. L. Stratton, A. Dong, M. Manning, and J. Carpenter, “Drug Delivery Matrix Containing Native Protein Precipitates Suspended in a Poloxamer Gel”, Journal of Pharmaceutical Sciences, Vol. 86, No. 9 September 1997, pp 1006-1110. E. Fattal, G. De Rosa, and A. Bochot, “Gel and solid matrix systems for controlled delivery of drug carrier-associated nucleic acids”, international Journal of Pharmaceutics,Vol. 277, 2004, pp 25-30. Biotechnology. (2009). Retrieved 03/01, 2010, from http://www.nibib.nih.gov.ezproxy.library.wisc.edu/Research/ResourceCenters/ListState Hudalla, G. A., Eng, T. S., & Murphy, W. L. (2008). An approach to modulate degradation and mesenchymal stem cell behavior in poly(ethylene glycol) networks. Biomacromolecules,9(3), 842-849. Hamidi, M., Azadi, A., & Rafiei, P. (2008). Hydrogelnanoparticles in drug delivery. Advanced Drug Delivery Reviews, 60(15), 1638-1649. Djalilian, A., Hamrah, P., & Pflugfelder, S. (2005). Disorders of tear production and the lacrimal unit. In J. Krachmer, M. Mannis & J. Hollan (Eds.), Cornea: Fundamentals, diagnosis and management (Second ed., pp. 521) Elsevier Mosby. Lemp, M. L., MD, & Foulks, G. N., MD. (2008). The definition & classification of dry eye disease. Guidlinesfrom the 2007 International Dry Eye Workshop, (April 2008), 1-6. Sjögren's syndrome foundation.
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