Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

Abstract

Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system. Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na+] and [AOT−Na+]-. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution.

Determining the protein drug release characteristics and cell adhesion to a PLLA or PLGA biodegradable polymer membrane

“…(Note: There are four tryptophan residues in KGF (http://ca.expasy.org/sprot/)). These films were also analyzed by ToF‐SIMS to determine the accumulation of AOT to the surface of the polymer, the results of this study was found by Burns and Gardella 21…”

“…ToF SIMS was used to learn the extent of AOT removal in the material, balancing with the potential degradation of the PLLA and PLGA during the washing treatments. As in previous work, CN and OCN were used to track protein distribution within the membrane 21. The instrument that was used in this study is equipped with a C 60 polyatomic ion source that can be operated as a sputtering gun during depth profile analysis.…”

Observation of the absorption of the In‐DTPA‐hexa–lactoside (IDHL) and its distribution in vitro by ICP‐MS and TOF‐SIMS

“…Then, the wafers were frozen quickly. The two wafers were brushed aside vertically (freeze fracture) in liquid nitrogen and dried by freeze‐dryer vacuum. The frozen‐dried samples were used for TOF‐SIMS analysis.…”

Differential orientation and conformation of surface-bound keratinocyte growth factor on (hydroxyethyl)methacrylate, (hydroxyethyl)methacrylate/methyl methacrylate, and (hydroxyethyl)methacrylate/methacrylic acid hydrogel copolymers

“…[4][5][6] Hydrogels for biomaterial-based delivery allow for localized, controlled, and extended delivery. [7][8][9][10][11] Upon traumatic injury, the epithelium initiates an intraepithelial repair process which involves the expression of mitogenic and motogenic proteins such as KGF. 11 Prior work from our labs and other labs has shown that exogenous addition of KGF in in vitro and in vivo wound models can expedite the wound closure process.…”