title: Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications.
abstract: The feasibility of various cellulose polymer derivatives, including methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), sodium-carboxymethylcellulose (sodium-CMC), and cationic-hydroxyethylcellulose (cationic-HEC), for use as an excipient to enhance drug delivery in nasal spray formulations was investigated. Three main parameters for evaluating the polymers in nasal drug delivery applications include rheology, ciliary beat frequency (CBF), and permeation across nasal tissue. Reversible thermally induced viscosity enhancement was observed at near nasal physiological temperature when cellulose derivatives were combined with an additional excipient, poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) graft copolymer (PVCL-PVA-PEG). Cationic-HEC was shown to enhance acyclovir permeation across the nasal mucosa. None of the tested cellulosic polymers caused any adverse effects on porcine nasal tissues and cells, as assessed by alterations in CBF. Upon an increase in polymer concentration, a reduction in CBF was observed when ciliated cells were immersed in the polymer solution, and this decrease returned to baseline when the polymer was removed. While each cellulose derivative exhibited unique advantages for nasal drug delivery applications, none stood out on their own to improve more than one of the performance characteristics examined. Hence, these data may be useful for the development of new cellulose derivatives in nasal drug formulations.
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Kellisa
authors.initials: K
authors.lastname: Hansen
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Gwangseong
authors.initials: G
authors.lastname: Kim
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Kashappa-Goud H
authors.initials: KG
authors.lastname: Desai
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Hiren
authors.initials: H
authors.lastname: Patel
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Olsen
authors.forename: Jaime
authors.initials: J
authors.lastname: Curtis-Fisk
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tocce
authors.forename: Susan
authors.initials: S
authors.lastname: Jordan
authors.affiliation: †Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.|‡Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schwendeman
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000268:Adhesiveness; D000280:Administration, Inhalation; D000818:Animals; D002478:Cells, Cultured; D002482:Cellulose / Q000737:chemistry / Q000493:pharmacokinetics*; D002923:Cilia / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D012212:Rheology; D013552:Swine; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D011108:Polymers; D002482:Cellulose; D000212:Acyclovir
keywords: acyclovir; cellulose; mucoadhesion; nasal drug delivery; permeation enhancement; rheology; thermogelation