title: Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy.
abstract: Confocal Raman spectroscopy was implemented in a new label-free technique to quantify molecular diffusion coefficients within gels. A leading anti-HIV drug, tenofovir, was analyzed in a clinical microbicide gel. The gel was tested undiluted, and in 10%-50% wt/wt dilutions with vaginal fluid simulant to capture the range of conditions likely occurring in vivo. The concentration distributions of tenofovir in gel over time and space were measured and input to a mathematical diffusion model to deduce diffusion coefficients. These were 3.16 ± 0.11 × 10-6cm2/s in undiluted gel, and increased by 11%-46% depending on the extent of dilution. Results were interpreted with respect to traditional release rate measurements in devices such as Franz cells. This comparison highlighted an advantage of our assay in that it characterizes the diffusive barrier within the gel material itself; in contrast, release rate in the traditional assay is affected by external conditions, such as drug partitioning at the gel/liquid sink interface. This new assay is relevant to diffusion in polymeric hydrogels over pharmacologically relevant length scales, for example, those characteristic of topical drug delivery. Resulting transport parameters are salient measures of drug delivery potential, and serve as inputs to computational models of drug delivery performance.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708.
authors.forename: Oranat
authors.initials: O
authors.lastname: Chuchuen
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Maher
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708.
authors.forename: Morgan G
authors.initials: MG
authors.lastname: Simons
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Peters
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Wax
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708; Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina 27708. Electronic address: dkatz@duke.edu.
authors.forename: David F
authors.initials: DF
authors.lastname: Katz
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry; D004058:Diffusion; D065546:Drug Liberation; D005782:Gels / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods*; D000068698:Tenofovir / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D005782:Gels; D000068698:Tenofovir
keywords: HIV/AIDS; Raman spectroscopy; diffusion; drug delivery; drug transport; hydrogels; microbicides; pharmacokinetics; tenofovir