Compatibility of a protein topical gel with wound dressings.
The compatibility between several dressing materials and a recombinant human vascular endothelial growth factor (rhVEGF) topical methylcellulose gel formulation was investigated. The dressings being studied were Adaptic, Non-stick Dressing, Conformant 2, Opsite and Tegapore. The criteria to select a compatible dressing include protein stability, absence of leachables from the dressing, and ability to retain gel on wound. An LC-MS method with sample treatment using cellulase was developed to determine protein oxidation in gel formulations. Results showed that rhVEGF was significantly oxidized by Adaptic dressing in 24 h. Protein oxidation was likely due to the peroxides, as determined by FOX assay, released into the protein solution from the dressing. Furthermore, Adaptic dressing caused protein adsorption loss, formation of high MW protein adducts, and released leachables as determined by RP-HPLC, LC-MS, and SEC. No protein oxidation or loss was observed after exposure to the other four alternative dressings. However, unknown leachables were detected in the presence of Opsite and Non-stick Dressing. The pore sizes of the Conformant 2 and Non-stick dressings were too large to hold the topical gel within the wound area, making them unsuitable for patient use. No rhVEGF bioactivity loss was observed in the presence of Tegapore. In conclusion, Tegapore was considered suitable for the rhVEGF topical gel.
Ji
Junyan A
JA
Late Stage Pharmaceutical and Device Development, Process Research and Development, Genentech, Inc, South San Francisco, California 94080, USA. ji.junyan@gene.com
Borisov
Oleg
O
Ingham
Erika
E
Ling
Victor
V
Wang
Y John
YJ
D000268:Adhesiveness; D000279:Administration, Cutaneous; D001458:Bandages; D017438:Bisphenol A-Glycidyl Methacrylate / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D042783:Endothelial Cells / Q000187:drug effects; D004867:Equipment Design; D005782:Gels; D006801:Humans; D013058:Mass Spectrometry; D008747:Methylcellulose / Q000737:chemistry*; D010084:Oxidation-Reduction; D011140:Polyurethanes / Q000737:chemistry; D011489:Protein Denaturation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
D004337:Drug Carriers; D005782:Gels; C027324:Opsiture; D011140:Polyurethanes; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017438:Bisphenol A-Glycidyl Methacrylate; D008747:Methylcellulose