title: Hydrogen peroxide mediated transvaginal drug delivery.
abstract: Simple, safe and effective permeability enhancers are crucial for successful non-invasive drug delivery methods. We seek local permeability augmentation mechanisms for integration into passive or active architectures in order to enable novel therapeutic delivery routes of the target drug while minimizing drug formulation challenges. This study explores the efficacy of hydrogen peroxide (HP) as a permeability enhancer for transmucosal delivery of macromolecules. HP at low concentrations (2–8 mM) is an effective permeability enhancer that is locally metabolized and safe. HP improves drug permeation through mucosa by altering tight junctions (TJ) between cells and oxidizing enzymes that function to degrade the foreign species. Results from trans-epithelial electrical resistance measurements and cell viability assay show reversible disassembly of TJ with minimal cell damage demonstrating the feasibility of HP as a safe permeability enhancer for drug delivery. Permeation studies show that HP treatment of cell cultured vaginal mucosa significantly enhances the permeability to insulin by more than an order of magnitude. This work lays foundation for the development of a drug delivery platform that administers drug doses by enhancing the permeability of local epithelial tissue via a separate HP treatment step.
authors.affiliation: Palo Alto Research Center, 3333 Coyote Hill Rd., Palo Alto, CA 94304, United States. hfatakdawala@ucdavis.edu
authors.forename: Hussain
authors.initials: H
authors.lastname: Fatakdawala
authors.forename: Scott A
authors.initials: SA
authors.lastname: Uhland
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009092:Mucous Membrane / Q000378:metabolism; D010539:Permeability; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005079:Excipients; D007328:Insulin; D006861:Hydrogen Peroxide